Affinage

NPPC

C-type natriuretic peptide · UniProt P23582

Round 2 corrected
Length
126 aa
Mass
13.2 kDa
Annotated
2026-04-29
130 papers in source corpus 45 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPPC encodes C-type natriuretic peptide (CNP), a paracrine/autocrine signaling peptide that is proteolytically processed from a 126-amino acid precursor by furin and selectively activates the NPR-B (GC-B) guanylyl cyclase receptor to generate cGMP, with additional signaling through the clearance receptor NPR-C (PMID:1672777, PMID:12736257, PMID:1309330). In bone, CNP/NPR-B/cGMP signaling is essential for endochondral ossification by promoting chondrocyte proliferation and hypertrophy and antagonizing FGFR3-MAPK signaling; loss-of-function NPPC mutations cause short stature in humans and mice, while gain-of-function (overexpression) produces skeletal overgrowth (PMID:14702637, PMID:28661490, PMID:17373680, PMID:20610569). In the ovary, mural granulosa cell–derived CNP maintains oocyte meiotic arrest via cumulus cell NPR2/cGMP until the LH surge triggers EGFR–ERK1/2–dependent TTP-mediated degradation of Nppc mRNA, permitting meiotic resumption (PMID:20947764, PMID:34031239). In the cardiovascular system, CNP modulates cardiomyocyte contractility through PKG-mediated phosphorylation of troponin I and phospholamban, exerts antiarrhythmic effects by PDE2-dependent cAMP hydrolysis, relaxes vascular smooth muscle via PKG–BKCa channels, and suppresses macrophage-driven inflammation by enhancing PHD2–HIF-1α interaction through CD36-mediated endocytosis (PMID:33970224, PMID:36715019, PMID:17083062, PMID:38456298).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Cloning of the NPPC gene and its brain-restricted expression established CNP as a distinct member of the natriuretic peptide family with a potential CNS role, answering whether natriuretic peptides existed beyond ANP and BNP.

    Evidence cDNA cloning, sequencing, and Northern blot in rat tissues showing brain-only expression; parallel human gene characterization with peptide identification by HPLC-RIA

    PMID:1702395 PMID:2018508

    Open questions at the time
    • Full tissue distribution beyond brain not yet mapped
    • Receptor identity unknown
  2. 1991 High

    Demonstration that CNP selectively activates NPR-B (GC-B) rather than NPR-A resolved which receptor transduces CNP signals and defined the CNP–NPR-B–cGMP axis as the core signaling pathway.

    Evidence cGMP accumulation assays and binding competition in cells expressing recombinant human NPR-A vs. NPR-B; independent quantification of CNP's 50–500-fold selectivity

    PMID:1309330 PMID:1672777

    Open questions at the time
    • No structural basis for receptor selectivity
    • Role of NPR-C clearance receptor in CNP signaling unclear
  3. 1996 High

    Discovery that CNP stimulates cGMP in osteoblasts and promotes differentiation markers linked CNP to skeletal biology, opening the question of whether CNP regulates bone growth in vivo.

    Evidence cGMP, DNA synthesis, alkaline phosphatase, osteocalcin, and mineralization assays in rat calvarial osteoblasts; 8-bromo-cGMP mimicry

    PMID:8967430

    Open questions at the time
    • In vivo bone phenotype of CNP loss not yet established
    • Chondrocyte vs. osteoblast contributions unknown
  4. 1999 High

    Structural determination of the NPR-C–CNP complex revealed how a single CNP molecule induces asymmetric receptor closure, providing the first atomic-level view of natriuretic peptide receptor activation.

    Evidence X-ray crystallography at 2.0 Å resolution of NPR-C extracellular domain bound to CNP

    PMID:11533490

    Open questions at the time
    • NPR-B structure with CNP not yet solved
    • Mechanism of intracellular guanylyl cyclase activation upon ligand binding unresolved
  5. 2003 High

    Identification of furin as the endoprotease processing pro-CNP to mature CNP resolved how the NPPC precursor is activated, distinguishing CNP processing from corin-dependent ANP maturation.

    Evidence Furin inhibitor blockade, furin-deficient cell reconstitution, purified furin cleavage, and bioactivity assay in HEK293/LoVo cells

    PMID:12736257

    Open questions at the time
    • Whether other proprotein convertases contribute in specific tissues
    • Regulation of furin-mediated processing in vivo
  6. 2003 High

    Genetic rescue of achondroplasia-model mice by chondrocyte-specific CNP overexpression demonstrated that CNP opposes FGFR3-MAPK signaling in growth-plate chondrocytes, establishing the mechanistic basis for CNP's role in endochondral ossification.

    Evidence Transgenic CNP overexpression in FGFR3-activated mice; bone length measurement; pERK and STAT-1 Western blot

    PMID:14702637

    Open questions at the time
    • Direct cGMP-to-MAPK inhibition intermediates not identified
    • Downstream effectors of MAPK inhibition in chondrocytes uncharacterized
  7. 2007 High

    Human chromosomal translocations separating NPPC from a negative regulatory element caused CNP overexpression and skeletal overgrowth, directly linking NPPC dosage to human growth regulation and providing the first human genetic evidence for NPPC gain-of-function.

    Evidence FISH, array-CGH, breakpoint cloning, plasma CNP by RIA, NPPC mRNA in patient fibroblasts, plus transgenic mouse phenocopying

    PMID:17373680 PMID:17676597

    Open questions at the time
    • Identity of the distal negative regulatory element not determined
    • Whether NPPC copy number variation contributes to normal height variation
  8. 2008 High

    Characterization of the lbab hypomorphic Nppc mutation showed that a single conserved arginine in the CNP ring is critical for NPR-B binding, and chondrocyte-specific transgenic rescue proved the dwarfism is cartilage-autonomous.

    Evidence Radioligand competition binding, cGMP activation assays with mutant peptide, transgenic rescue, growth-plate histology

    PMID:18554750 PMID:18775416

    Open questions at the time
    • Full structural basis for the arginine–NPR-B interaction
    • Whether heterozygous Nppc mutations cause milder skeletal phenotypes in mice
  9. 2010 High

    Discovery that mural granulosa cell–derived CNP maintains oocyte meiotic arrest via cumulus cell NPR2/cGMP established a new paracrine signaling axis essential for female fertility, answering how follicles prevent premature meiotic resumption.

    Evidence Nppc and Npr2 knockout mice with precocious meiotic resumption; in situ hybridization; in vitro cGMP rescue; oocyte-derived factor regulation of NPR2

    PMID:20947764

    Open questions at the time
    • Mechanism of cGMP transfer from cumulus to oocyte not fully resolved
    • Identity of oocyte-derived factors regulating NPR2
  10. 2012 High

    Extension of the ovarian CNP model showed that amphiregulin (an EGFR ligand induced by LH) suppresses NPPC mRNA, defining the LH→EGFR→decreased NPPC→meiotic resumption pathway and explaining how the LH surge terminates CNP signaling.

    Evidence Amphiregulin treatment of granulosa cells; hCG in vivo; Npr2 mutant phenotyping at early antral stages; CNP analog therapeutic rescue in achondroplasia mice

    PMID:22696190 PMID:22987720 PMID:23200862

    Open questions at the time
    • Post-transcriptional mechanism of NPPC mRNA decay not yet identified at this time
    • Whether BNP contributes redundantly in porcine systems
  11. 2013 High

    Demonstration that CNP modulates cardiomyocyte contractility via PKG-mediated phosphorylation of phospholamban and troponin I, dependent on SERCA2, established the molecular basis for CNP's negative inotropic and positive lusitropic cardiac effects.

    Evidence Muscle strip contractility, Ca²⁺ transient imaging, PLB/TnI phosphorylation Western blot, SERCA2 cardiomyocyte-specific knockout mice, PKG inhibitors

    PMID:23808942

    Open questions at the time
    • Subcellular compartmentalization of CNP-stimulated cGMP not yet resolved
    • Relevance in human heart failure not yet tested
  12. 2017 High

    Identification of heterozygous loss-of-function NPPC mutations in patients with short stature provided the first direct human genetic evidence that NPPC haploinsufficiency causes growth impairment, completing the bidirectional dosage–phenotype relationship.

    Evidence NPPC sequencing in 668 patients, cGMP assay of mutant CNP peptides, family co-segregation

    PMID:28661490

    Open questions at the time
    • Prevalence of NPPC mutations among all short stature patients unclear
    • Whether therapeutic CNP analog could rescue human NPPC haploinsufficiency
  13. 2021 High

    Identification of TTP (ZFP36) as the mediator of LH-induced Nppc mRNA degradation via a non-canonical AU-rich element resolved the post-transcriptional mechanism by which the LH surge terminates CNP production and permits oocyte meiotic resumption.

    Evidence MGC-specific Zfp36 conditional knockout; lentiviral knockdown; TTP–Nppc 3′ UTR RNA-binding assay; EGFR-ERK inhibitor pathway dissection; oocyte meiotic phenotyping

    PMID:34031239

    Open questions at the time
    • Whether additional RNA-binding proteins contribute to Nppc mRNA regulation
    • Chromatin-level regulation of NPPC transcription during the LH surge
  14. 2022 High

    Subcellular FRET biosensor imaging revealed that CNP uniquely increases cGMP near both troponin I and phospholamban (unlike BNP), explaining the differential cardiac functional effects of NPR-B vs. NPR-A signaling and their modulation by PDE2/PDE3.

    Evidence Targeted cGMP FRET biosensors (PLB- and TnI-targeted); SICM local stimulation; PDE inhibitors; comparison of CNP vs. BNP in sham and heart failure cardiomyocytes

    PMID:33970224

    Open questions at the time
    • Whether compartmentalized signaling differs in human vs. rodent cardiomyocytes
    • Role of NPR-B membrane localization in cGMP compartmentalization
  15. 2023 High

    Discovery that CNP's antiarrhythmic action operates through PDE2 activation (cGMP→PDE2→cAMP hydrolysis→reduced ICaL, INaL, and Ca²⁺ sparks) defined a cGMP-to-cAMP cross-talk mechanism confirmed by cardiomyocyte-specific PDE2 deletion and human iPSC-CMs.

    Evidence Ex vivo ischemia/reperfusion arrhythmia model; in vivo catecholamine challenge; patch-clamp; Ca²⁺ spark imaging; cardiomyocyte-specific PDE2 KO; human iPSC-CMs

    PMID:36715019

    Open questions at the time
    • Whether chronic CNP supplementation provides sustained antiarrhythmic protection
    • Interaction between PDE2 and PDE3 pathways at therapeutic CNP doses
  16. 2024 High

    Identification of CD36 as a macrophage CNP receptor mediating endocytosis and the PHD2–HIF-1α degradation mechanism expanded CNP's role to anti-inflammatory and anti-atherogenic signaling independent of canonical NPR-B/cGMP.

    Evidence Co-IP for PHD2–HIF-1α interaction; CD36 KO macrophages; endocytosis assay; CNP infusion and genetic overexpression in ApoE⁻/⁻ mice; plaque quantification

    PMID:38456298

    Open questions at the time
    • Whether CD36-mediated CNP signaling occurs in non-macrophage cell types
    • How intracellular CNP (post-endocytosis) physically enhances PHD2–HIF-1α binding
    • Independence from NPR-B or NPR-C requires further confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for CNP–NPR-B activation (no co-crystal structure), the identity of the distal negative regulatory element controlling NPPC transcription, the full spectrum of CNP's CNS functions beyond axon bifurcation, and whether CD36-mediated CNP signaling operates independently of canonical natriuretic peptide receptors in vivo.
  • No NPR-B–CNP co-crystal structure available
  • Distal NPPC regulatory element not molecularly characterized
  • CNS functions beyond sensory axon bifurcation poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1474165 Reproduction 4 R-HSA-168256 Immune System 3 R-HSA-112316 Neuronal System 1 R-HSA-392499 Metabolism of proteins 1
Partners
CD36FGFR3FURINNPR2NPR3PDE2AZFP36

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CNP (encoded by NPPC) selectively and potently activates the ANPR-B (NPR-B/GC-B) guanylyl cyclase receptor, with 50- to 500-fold higher affinity for NPR-B than ANP or BNP respectively, and does not stimulate cGMP accumulation via ANPR-A (NPR-A/GC-A). Cell-based cGMP accumulation assay and receptor binding competition in cells expressing recombinant human ANPR-A or ANPR-B Science High 1672777
1991 Human NPPC encodes a 126-amino acid prepro-CNP precursor processed to yield CNP-22 and CNP-53; the gene contains at least two exons and one intron, with a 5'-flanking region containing an inverted CCAAT box, two GC boxes, and a cAMP response element-like sequence distinct from ANP and BNP gene promoters. Genomic library cloning, sequencing, and cDNA structure analysis; HPLC-RIA for peptide identification in human brain Biochemical and biophysical research communications High 2018508
1991 CNP-like immunoreactivity is highest in the anterior pituitary and present throughout the brain, with tissue distribution and processing pattern (yielding CNP and CNP-53) clearly different from ANP and BNP, consistent with a role as a neuropeptide/neuromodulator rather than a cardiac hormone. Specific radioimmunoassay (RIA) for CNP, HPLC-gel permeation chromatography to resolve molecular forms in rat and human tissues Endocrinology High 1855454
1990 Rat NPPC encodes a 126-residue precursor with a 23-residue signal sequence; CNP mRNA is expressed exclusively in the brain (by Northern blot), suggesting CNP functions as a CNS neuropeptide. cDNA library cloning, sequencing, RNA blot hybridization FEBS letters High 1702395
1990 CNP potently increases cGMP levels and stimulates guanylate cyclase activity in the particulate fraction of rat vascular smooth muscle cells (VSMC), with maximum activation 4-fold higher than ANP, establishing CNP as a potent cGMP stimulator specifically in VSMC. Cell-based cGMP measurement, guanylate cyclase activity assay in particulate fraction of cultured rat VSMC Biochemical and biophysical research communications High 2164803
1992 CNP binds with highest affinity to NPR-B (GC-B) and activates cGMP production via NPR-B with rank order CNP > ANP ≥ BNP; CNP binds NPR-C clearance receptor with intermediate affinity (ANP > CNP > BNP); species differences exist in receptor selectivity, particularly for BNP. Radioligand binding competition assays and cGMP production assays using receptor preparations from human, bovine, and rat tissues and cultured cells; Northern blot for receptor expression Endocrinology High 1309330
1992 Human NPPC gene is located on chromosome 2 (later refined to 2q37.1) and encodes a 126-amino acid prepro-CNP; the 5'-flanking region contains cis-regulatory elements (inverted CCAAT box, GC boxes, cAMP response element-like sequence) absent in ANP and BNP gene promoters. CNP is the dominant natriuretic peptide in human brain. Genomic cloning, sequencing, somatic hybrid cell chromosome mapping, HPLC-RIA for peptide identification in human brain Hypertension High 1339402
1993 CNP is the major natriuretic peptide in human cerebrospinal fluid (CSF), present at ~10-fold higher concentration than ANP or BNP in CSF, while CNP is undetectable in plasma, supporting a primary CNS paracrine/autocrine role for NPPC-derived CNP. Specific radioimmunoassay (RIA) measurement of ANP, BNP, and CNP in matched CSF and plasma samples from patients Brain research High 8330189
1994 Mouse NPPC (Nppc) gene maps to chromosome 1, is composed of at least two exons and one intron, with conserved 5'-flanking regulatory elements; comparison with human NPPC reveals conserved and divergent regions. Human NPPC maps to chromosome 2. Genomic library cloning, sequencing, PCR-based microsatellite polymorphism analysis in recombinant inbred mouse strains, somatic hybrid cell chromosome mapping Genomics High 7698765
1994 CNP is produced in the anterior pituitary predominantly by gonadotropes (co-localized with LH); pituitary cells express GC-B (NPR-B) but not GC-A; CNP potently stimulates cGMP in gonadotropes, suggesting an autocrine role. Selective destruction of gonadotropes reduced both CNP-stimulated cGMP production and GnRH-stimulated LH release. RT-PCR for CNP precursor mRNA, immunohistochemistry with co-localization of CNP and LH, targeted toxin (GnRH-ricin A conjugate) to selectively ablate gonadotropes, cGMP accumulation assay Endocrinology High 7988473
1996 CNP stimulates cGMP production in osteoblast-like cells via NPR-B, inhibits DNA synthesis in a dose-dependent manner, and promotes osteoblast differentiation markers (alkaline phosphatase activity, osteocalcin mRNA, mineralization); these effects are mimicked by 8-bromo-cGMP, establishing a cGMP-mediated signaling pathway for CNP in bone formation. CNP-like immunoreactivity is detected in conditioned medium from osteoblasts. cGMP accumulation assay, DNA synthesis (thymidine incorporation), alkaline phosphatase activity assay, Northern blot for gene expression, mineralization nodule quantification in cultured rat calvarial osteoblasts American journal of physiology High 8967430
1995 Shear stress (24 dyne/cm²) markedly induces NPPC mRNA expression in human umbilical vein endothelial cells within 3 hours, maintained through 12 hours, identifying hemodynamic flow as a transcriptional regulator of CNP gene expression. Cone-plate viscometer shear stress exposure of HUVEC; CNP mRNA quantification by RT-PCR FEBS letters Medium 7589445
1999 Shear stress induction of NPPC mRNA in endothelial cells is independent of NO autocrine signaling (not blocked by L-NAME or genistein) but is attenuated 71% by intracellular calcium chelation (BAPTA/AM), implicating calcium-dependent signaling in flow-mediated CNP transcriptional regulation. Dexamethasone potentiates shear-stress-induced CNP mRNA 2-fold. Defined laminar shear stress (25 dyn/cm²) of bovine aortic endothelial cells; PhosphorImager quantification of CNP/GAPDH mRNA ratio; pharmacological inhibition of NO synthase, tyrosine kinase, calcium signaling; CNP secretion measurement by RIA Annals of biomedical engineering Medium 10468226
2001 Crystal structure of NPR-C extracellular domain bound to CNP reveals that a single CNP molecule binds asymmetrically at the interface of a symmetric NPR-C dimer, inducing a 20 Å closure between membrane-proximal domains; each monomer contains a molecular spring (linker peptide) that is an allosteric trigger for intracellular signaling. X-ray crystallography at 2.9 Å (unliganded) and 2.0 Å (CNP-bound) resolution; hormone-binding thermodynamics Science High 11533490
2003 Furin is the critical intracellular endoprotease responsible for processing pro-CNP to mature CNP. Pro-CNP processing is blocked by furin inhibitors, absent in furin-deficient LoVo cells, and restored by recombinant furin expression; corin (the ANP convertase) does not process pro-CNP. Furin-processed CNP is biologically active in cGMP assays. Recombinant expression in HEK293 and SW1353 cells; furin inhibitor treatment; expression in furin-deficient LoVo cells with reconstitution; incubation with purified recombinant furin; Western blot; cell-based cGMP bioassay Journal of Biological Chemistry High 12736257
2003 CNP overexpression in chondrocytes rescues dwarfism in achondroplasia mice (activated FGFR3) by correcting decreased extracellular matrix synthesis in the growth plate through inhibition of the MAPK pathway of FGF signaling; CNP does not affect the STAT-1 pathway of FGFR3 signaling. Transgenic chondrocyte-specific CNP overexpression in FGFR3-activated achondroplasia mouse model; bone length measurement; immunohistochemistry; Western blot for phospho-ERK (MAPK) and STAT-1 pathway markers Nature Medicine High 14702637
2004 CNP inhibits endothelin-1 (ET-1)-induced cardiac myocyte hypertrophy via a cGMP-dependent mechanism, suppressing protein synthesis, ANP secretion, GATA-4/MEF-2 DNA binding, CaM kinase II activity, ERK phosphorylation, and intracellular Ca²⁺ increase. Conversely, ET-1 suppresses CNP-induced cGMP accumulation through a protein kinase C- and Ca²⁺-dependent mechanism, establishing mutual interference between CNP and ET-1 signaling pathways. Cultured neonatal rat cardiac myocytes; protein synthesis assay (³H-leucine), ANP secretion RIA, EMSA for transcription factor binding, CaM kinase II activity assay, ERK phosphorylation by Western blot, intracellular Ca²⁺ imaging, cGMP measurement; 8-bromo-cGMP as mechanistic probe; PKC activator and Ca²⁺ ionophore experiments Endocrinology High 14749356
2007 Overexpression of NPPC (due to balanced translocation disrupting a negative regulatory element on chromosome 2q37.1) leads to doubled plasma CNP concentration and a Marfanoid overgrowth phenotype in humans; transgenic mice with NPPC overexpression in bone recapitulate this phenotype, directly linking elevated CNP levels to skeletal overgrowth. FISH and array-CGH characterization of translocation; breakpoint cloning and sequencing; plasma CNP measurement by RIA; NPPC mRNA quantification in patient fibroblasts; phenotype analysis of NPPC-overexpressing transgenic mice Human Mutation High 17373680
2007 A cluster of translocation breakpoints near NPPC in 2q37.1 causes NPPC overexpression in multiple patients with similar overgrowth phenotype, consistent with separation from a negative regulatory element on chromosome 2 as the causative mechanism. Cytogenetic analysis, molecular breakpoint characterization, NPPC expression quantification in patient-derived cells Human Mutation Medium 17676597
2008 The lbab mouse mutation (R-to-G substitution in conserved CNP coding region) causes dwarfism by reducing CNP's ability to bind and activate NPR-B: 10-fold more CNP(lbab) is required to compete for receptor binding, and 30- to >100-fold more is required to activate NPR-B in cGMP assays. Molecular modeling suggests the conserved arginine is critical for binding an acidic pocket in NPR-B. Whole-cell cGMP elevation assay, membrane guanylyl cyclase activity assay, radioligand competition binding with [¹²⁵I]CNP, molecular modeling Peptides High 18554750
2008 The lbab/lbab mouse spontaneous mutation is a hypomorphic Nppc mutation retaining only slight CNP activity for cGMP production; transgenic rescue with chondrocyte-specific CNP expression fully compensates the dwarf phenotype, confirming NPPC loss-of-function causes dwarfism through impaired endochondral ossification with markedly reduced proliferative and hypertrophic chondrocyte zones. Transgenic rescue experiment; cGMP production assay for lbab CNP activity; histological analysis of growth plate; bone length measurement Biochemical and biophysical research communications High 18775416
2009 CNP acts as a bifurcation factor for sensory neurons: CNP activates a cGMP signaling cascade via NPR2 (GC-B) that is essential for sensory axon bifurcation at the dorsal root entry zone (DREZ) of the spinal cord, but does not affect collateral formation. In CNP mutant mice, bifurcation errors persist at maturity and result in reduced synaptic input on secondary neurons (measured by patch-clamp). CNP knockout mouse analysis; axon tracing; electrophysiological patch-clamp recordings; genetic comparison with nitric oxide-sensitive guanylyl cyclase (NO-GC) knockouts Proceedings of the National Academy of Sciences High 19805384
2010 Mural granulosa cells express NPPC mRNA while cumulus cells express NPR2 (GC-B); CNP increases cGMP in cumulus cells and oocytes and inhibits meiotic resumption in vitro. Graafian follicles of Nppc or Npr2 mutant mice fail to sustain meiotic arrest, with precocious meiotic resumption. Oocyte-derived paracrine factors promote cumulus cell NPR2 expression, establishing a granulosa→cumulus→oocyte paracrine signaling axis. In situ hybridization and RT-PCR for Nppc/Npr2 expression; cGMP measurement in cumulus cells and oocytes; in vitro meiosis inhibition assay; Nppc and Npr2 knockout mouse phenotyping; conditioned medium experiments with oocyte-derived factors Science High 20947764
2010 The local CNP/GC-B system within the growth plate is responsible for physiological endochondral bone growth: cartilage-specific Nppc or GC-B knockout mice have severely shortened bones comparable to systemic knockouts, with drastically reduced hypertrophic chondrocyte layers and moderately reduced proliferative layers. Circulating CNP from transgenic mice with liver-specific NPPC overexpression can rescue impaired bone growth and reduce mortality of CNP knockout mice, demonstrating that systemic CNP delivery is sufficient. Cartilage-specific conditional knockout mice for Nppc and NPR2 (GC-B); bone length measurement; histological growth plate analysis; BrdU proliferation assay; rescue by SAP-Nppc transgenic mice (systemic CNP); survival analysis Endocrinology / Scientific Reports High 20610569 26014585
2011 The pre-ovulatory LH/hCG surge decreases CNP secretion by granulosa cells to promote meiotic resumption: LH/hCG treatment decreases NPPC transcripts in mural granulosa cells and ovarian CNP content; CNP treatment of cumulus-oocyte complexes inhibits meiosis resumption with increased cGMP in both cumulus cells and oocytes. In human ovaries, CNP in follicular fluid decreases following ovulatory hCG dose. Genome-wide microarray analysis of periovulatory ovaries; RT-PCR quantification of NPPC; RIA for ovarian CNP; in vitro meiosis inhibition assay; cGMP measurement; human follicular fluid CNP measurement Human Reproduction High 21865234
2012 CNP/NPR2 signaling maintains oocyte meiotic arrest from early antral follicle stages; Npr2 mutant mice show precocious meiotic resumption in early antral follicles. Amphiregulin (an LH/hCG mediator acting via EGFR) suppresses NPPC mRNA levels in cultured granulosa cells, establishing the LH→EGFR→amphiregulin→decreased NPPC→meiotic resumption pathway. In situ hybridization and RT-PCR for Nppc/Npr2 in ovaries at different follicular stages; histological phenotyping of Npr2 mutant mice; hCG treatment of immature mice with quantification of NPPC mRNA; amphiregulin treatment of cultured granulosa cells Molecular Reproduction and Development High 22987720
2012 NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation: Nppc(lbab) and Npr2(cn) mutant mice ovulate oocytes with fragmented/degenerated ooplasm that fail to develop past the two-cell stage; oocytes in antral follicles prematurely resume meiosis with disorganized chromosomes; ovulated oocytes lack cumulus cells. Phenotypic analysis of Nppc and Npr2 mutant mice; histology of ovaries; oocyte developmental competence assay (fertilization and two-cell development) Reproduction High 22696190
2012 A CNP analog (BMN 111) resistant to neutral endopeptidase (NEP) degradation inhibits MAPK pathway activation (decreased pERK1/2) in human achondroplasia growth-plate chondrocytes and rescues bone growth in Fgfr3(Y367C/+) achondroplasia mice, confirming the CNP→NPR-B→cGMP→MAPK inhibition mechanism as therapeutically relevant. ERK1/2 phosphorylation assay in human achondroplasia chondrocytes; bone growth measurement in Fgfr3 mutant mice treated with BMN 111; skeletal analysis including growth plate histology American Journal of Human Genetics High 23200862
2013 CNP infusion in failing rat hearts increases cGMP and produces a negative inotropic response (NIR) and positive lusitropic response (LR) via PKG-mediated phosphorylation of phospholamban (PLB Ser16) and troponin I (TnI Ser23/24); SERCA2 activity is essential for both responses, as shown by SERCA inhibition (thapsigargin) and cardiomyocyte-specific SERCA2 gene inactivation. CNP increases Ca²⁺ transient amplitude and SERCA2 activity. Muscle strip contractility measurements; cGMP level assay; Ca²⁺ transient imaging; Western blot for PLB and TnI phosphorylation; SERCA inhibitor (thapsigargin) experiments; cardiomyocyte-specific SERCA2 knockout mice; PKG blocker experiments British Journal of Pharmacology High 23808942
2015 The local CNP/GC-B system in the growth plate is responsible for physiological endochondral bone growth; cartilage-specific GC-B (NPR-B) knockout mice are shorter than cartilage-specific CNP knockout mice, indicating that GC-B in the growth plate may also respond to signals beyond local CNP. Cartilage-specific conditional knockout mice for Nppc and NPR2 (GC-B); bone length measurement; growth plate histology; comparison with systemic knockouts; BrdU proliferation assay Scientific Reports High 26014585
2017 Two heterozygous NPPC mutations in the conserved CNP ring region cause autosomal dominant short stature in humans; both mutations show significant reductions in cGMP synthesis when tested functionally, confirming loss-of-function pathogenicity. One mutation corresponds to the lbab mouse mutation. NPPC sequencing in 668 patients (357 disproportionate short stature, 311 ISS) plus exome sequencing; cGMP production assay for functional validation of mutant CNP peptides; co-segregation analysis in families Genetics in Medicine High 28661490
2017 Elevated circulatory CNP (from liver-specific NPPC transgenic mice) rescues craniofacial hypoplasia in achondroplasia (Fgfr3ach) mice by restoring spheno-occipital synchondrosis thickness, promoting chondrocyte proliferation in craniofacial cartilage, and ameliorating foramen magnum stenosis, demonstrating that systemic CNP promotes endochondral ossification in craniofacial as well as appendicular bone. Fgfr3ach mice crossed with SAP-Nppc-Tg mice (systemic CNP); craniofacial morphometric analysis; synchondrosis histology; chondrocyte proliferation assay Journal of Dental Research High 28644737
2021 Tristetraprolin (TTP/ZFP36) mediates LH-surge-induced degradation of Nppc mRNA in mural granulosa cells: LH/hCG transiently upregulates Zfp36 mRNA; TTP directly targets a rare non-canonical AU-rich element in the Nppc 3' UTR to destabilize Nppc mRNA; MGC-specific Zfp36 knockout and lentiviral knockdown impair LH-induced Nppc mRNA decline and oocyte meiotic resumption. LH activates Zfp36/TTP via the EGFR-ERK1/2-dependent pathway. Gain- and loss-of-function of Zfp36 in MGCs; MGC-specific Zfp36 conditional knockout mice; in vivo lentiviral knockdown; RNA-binding assay (TTP binding to Nppc 3' UTR); mRNA stability assay; oocyte meiotic resumption phenotyping; pathway dissection with EGFR-ERK inhibitors Proceedings of the National Academy of Sciences High 34031239
2022 CNP, but not BNP, increases cGMP near troponin I (TnI) in addition to phospholamban (PLB) in adult cardiomyocytes, explaining the differential ability of CNP (vs. BNP) to induce both lusitropic and negative inotropic responses. CNP stimulation in t-tubules and on the cell crest both increase cGMP near TnI and PLB similarly; PDE2 and PDE3 constrain cGMP in both compartments. In heart failure cardiomyocytes, CNP increases cGMP near PLB and TnI more than in sham cells. FRET-based targeted cGMP biosensors (PLB-targeted and TnI-targeted); scanning ion conductance microscopy (SICM) for local receptor stimulation; ventricular strip contractility measurements; PDE2/PDE3 inhibitor experiments; comparison of CNP vs. BNP in normal and heart failure rat cardiomyocytes Cardiovascular Research High 33970224
2023 CNP exerts antiarrhythmic effects via PDE2 (phosphodiesterase 2): CNP-stimulated cGMP activates PDE2, which hydrolyzes cAMP, reducing catecholamine-mediated arrhythmogenic events, ICaL, INaL, and Ca²⁺ spark frequency. PDE2 inhibition or cardiomyocyte-specific PDE2 deletion abolishes CNP's antiarrhythmic effect. These findings were confirmed in human iPSC-derived cardiomyocytes. Ex vivo perfused mouse hearts (arrhythmia after ischemia/reperfusion); in vivo catecholamine injection in mice; patch-clamp (ICaL, INaL); Ca²⁺ spark imaging; cAMP level measurement; protein phosphorylation (Western blot); cardiomyocyte-specific PDE2 knockout mice; pharmacological PDE2 inhibition; human iPSC-derived cardiomyocytes Circulation Research High 36715019
2024 CNP promotes anti-inflammatory macrophage phenotype, efferocytosis, and reduces foam cell formation and necroptosis in atherosclerosis; mechanistically, CNP accelerates HIF-1α degradation by enhancing the interaction between PHD2 (prolyl hydroxylase domain-containing protein 2) and HIF-1α. CD36 binds CNP on the macrophage surface and mediates its endocytosis. CNP supplementation or overexpression reduces atherosclerotic plaque formation in ApoE-/- mice. Proteomics; co-immunoprecipitation (PHD2-HIF-1α interaction); CD36 knockout primary macrophages; endocytosis assay; CNP osmotic pump infusion and genetic overexpression in ApoE-/- mice; LCZ696 (neprilysin inhibitor) treatment; plaque analysis; macrophage functional assays (efferocytosis, foam cell formation, necroptosis) Circulation Research High 38456298
1999 Cloned ancestral shark NPR-B receptor activated by CNP increases cGMP (EC50 12 nM) and activates CFTR Cl⁻ channels (EC50 8 nM) when co-expressed in Xenopus oocytes with human CFTR, providing direct evidence that NPR-B/cGMP signaling activates CFTR; CNP increases oocyte cGMP 36-fold and Cl⁻ current 37-fold. Xenopus oocyte co-expression system; cGMP measurement; two-electrode voltage-clamp electrophysiology for Cl⁻ current measurement; receptor cloning and sequence analysis American Journal of Physiology High 9950772
1997 CNP activates CFTR-dependent Cl⁻ transport in vivo in mouse nasal airway epithelium via membrane-bound guanylate cyclase activation; CNP effect is absent in CFTR-null mice and present in ΔF508 CFTR mice where CNP plus forskolin synergistically stimulates Cl⁻ secretion. In vivo nasal transepithelial potential difference (TEPD) assay in wild-type, CFTR-/-, and CFTR(ΔF/ΔF) mice; 8-Br-cGMP as positive control; pharmacological dissection American Journal of Physiology High 9374736
1999 NPR-C receptor activation by CNP (mimicked by selective NPR-C agonist cANF4-23) suppresses leukocyte rolling on venular endothelium and reduces P-selectin expression on endothelial cells, leukocytes, and platelets; CNP also inhibits thrombin-induced platelet aggregation. These anti-inflammatory effects are mediated at least in part through NPR-C-dependent suppression of P-selectin. Intravital microscopy of mouse mesenteric venules (eNOS-/- mice and IL-1β/histamine-induced inflammation); selective NPR-C agonist (cANF4-23) comparison; platelet aggregation assay of human blood; P-selectin expression analysis in HUVEC, leukocytes, and platelets Proceedings of the National Academy of Sciences High 16179391
2013 2q37 deletions including the NPPC gene cause short stature with normal plasma CNP, while deletions that interrupt only the DIS3L2 gene (without involving NPPC) but are associated with elevated plasma CNP cause Marfanoid overgrowth, supporting that NPPC gene dosage directly determines CNP levels and skeletal growth outcome. Array CGH; NPPC gene copy number analysis; plasma CNP measurement by RIA; clinical phenotyping PLOS ONE Medium 23805197
2005 CNP inhibits leukocyte-endothelial interactions and platelet activation via suppression of P-selectin expression; this effect is mediated through NPR-C (not NPR-B/cGMP), as selective NPR-C agonist cANF4-23 mimics CNP's effect. Intravital microscopy; selective receptor agonists; P-selectin expression assay in HUVEC and blood cells; platelet aggregometry Proceedings of the National Academy of Sciences High 16179391
2005 CNP suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo in a rabbit carotid artery collar model of intimal hyperplasia; both peri-arterial and intra-luminal CNP reduce PAI-1 in endothelium, adventitia, and neointima, and reduce macrophage infiltration, independently of superoxide. Rabbit carotid collar model; immunohistochemistry and densitometry for PAI-1; Western blot; peri-arterial and intra-luminal CNP delivery; superoxide chemiluminescence assay Cardiovascular Research Medium 15914122
2006 CNP (but not ANP or BNP) relaxes human isolated subcutaneous resistance arteries via cGMP-dependent kinase (PKG) activation and opening of large-conductance Ca²⁺-activated potassium (BKCa) channels; this effect is endothelium-independent and not mediated by nitric oxide or soluble guanylate cyclase. Isometric myograph measurements on human subcutaneous resistance arteries; endothelium removal; NOS inhibition (L-NAME); soluble GC inhibitor (ODQ); PKG blocker (Rp-8-Br-cGMPS); high K⁺ and iberiotoxin (BKCa blocker); vasopeptidase inhibitor omapatrilat Journal of the Renin-Angiotensin-Aldosterone System High 17083062
2003 CNP inhibits spontaneous contraction of guinea pig caecal circular smooth muscle cells via cGMP-dependent activation of calcium-activated potassium currents (IK(ca)), including spontaneous transient outward currents (STOCs); both soluble and particulate guanylate cyclase pathways contribute to CNP-induced relaxation. Smooth muscle strip contractility recording; whole-cell patch-clamp for IK(ca) and membrane potential; guanylate cyclase inhibitors (LY83583); cGMP phosphodiesterase inhibitor (zaparinast); TEA as non-selective K⁺ channel blocker World Journal of Gastroenterology Medium 12970905
2017 Bovine NPR2 is expressed not only in cumulus cells (as in mouse/porcine) but also in oocyte membranes; CNP can directly activate intra-oocyte cGMP production via NPR2 on the oocyte membrane in addition to the cumulus cell-mediated pathway, representing a species-specific mechanism. NPR2 expression in bovine CCs and oocytes is synergistically regulated by estradiol and oocyte-derived growth factors. Immunofluorescence localization of NPR2 in bovine COCs; cGMP measurement in isolated oocytes after CNP treatment; comparison with mouse and porcine; gene expression analysis Theriogenology Medium 29080478
2014 LH and amphiregulin (an EGF-like peptide acting via EGFR) decrease BNP and CNP (NPPC) production in porcine granulosa cells and downregulate NPR2 expression in cumulus cells, together reducing oocyte cGMP to permit meiotic resumption; the effect of AREG on natriuretic peptide signaling and oocyte maturation is completely blocked by EGFR kinase inhibitor AG1478, while LH effect is only partially reversed. Porcine granulosa cell culture; COC co-culture with granulosa cells; EGFR inhibitor (AG1478); RT-PCR and ELISA for NPPC/BNP and NPR2 expression; cGMP measurement; oocyte maturation assay Molecular Reproduction and Development Medium 25348585

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 1451 20881960
1991 Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). Science (New York, N.Y.) 731 1672777
1992 Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology 696 1309330
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Many sequence variants affecting diversity of adult human height. Nature genetics 520 18391951
2010 Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science (New York, N.Y.) 454 20947764
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1993 Natriuretic peptide system in human heart failure. Circulation 375 8353861
1991 C-type natriuretic peptide (CNP) in rats and humans. Endocrinology 310 1855454
2003 Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nature medicine 303 14702637
1990 Cloning and sequence analysis of a cDNA encoding a precursor for rat C-type natriuretic peptide (CNP). FEBS letters 194 1702395
2003 Furin-mediated processing of Pro-C-type natriuretic peptide. The Journal of biological chemistry 167 12736257
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2012 Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. American journal of human genetics 153 23200862
2017 Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin. Cell reports 151 28076777
2011 Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides. Journal of cardiology 148 21296556
2001 Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone. Science (New York, N.Y.) 146 11533490
2005 Process outgrowth in oligodendrocytes is mediated by CNP, a novel microtubule assembly myelin protein. The Journal of cell biology 138 16103231
1991 Extracellular domain-IgG fusion proteins for three human natriuretic peptide receptors. Hormone pharmacology and application to solid phase screening of synthetic peptide antisera. The Journal of biological chemistry 125 1660465
2011 Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes. Human reproduction (Oxford, England) 118 21865234
1991 Gene and precursor structures of human C-type natriuretic peptide. Biochemical and biophysical research communications 115 2018508
1990 Novel natriuretic peptide, CNP, potently stimulates cyclic GMP production in rat cultured vascular smooth muscle cells. Biochemical and biophysical research communications 110 2164803
2007 Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation. Human mutation 102 17373680
2019 C-type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature. International journal of molecular sciences 100 31072047
1996 cGMP produced in response to ANP and CNP regulates proliferation and differentiation of osteoblastic cells. The American journal of physiology 98 8967430
1999 Myelin glycosphingolipid/cholesterol-enriched microdomains selectively sequester the non-compact myelin proteins CNP and MOG. Journal of neurocytology 88 10739571
2005 C-type natriuretic peptide and guanylyl cyclase B receptor. Peptides 86 15911070
2005 C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression. Proceedings of the National Academy of Sciences of the United States of America 83 16179391
2009 Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 81 19086053
2009 Regional release and clearance of C-type natriuretic peptides in the human circulation and relation to cardiac function. Hypertension (Dallas, Tex. : 1979) 81 19620509
1993 Detection of C-type natriuretic peptide (CNP) transcript in the rat heart and immune organs. Endocrinology 80 8462485
2014 Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. Human molecular genetics 77 25429064
2012 CNP/NPR2 signaling maintains oocyte meiotic arrest in early antral follicles and is suppressed by EGFR-mediated signaling in preovulatory follicles. Molecular reproduction and development 75 22987720
1992 Human C-type natriuretic peptide. Characterization of the gene and peptide. Hypertension (Dallas, Tex. : 1979) 75 1339402
2004 Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways. Endocrinology 74 14749356
2007 Osteocrin is a specific ligand of the natriuretic Peptide clearance receptor that modulates bone growth. The Journal of biological chemistry 73 17951249
1997 CNP overexpression induces aberrant oligodendrocyte membranes and inhibits MBP accumulation and myelin compaction. Journal of neuroscience research 72 9373033
2009 A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation. Human molecular genetics 71 19570815
1993 C-type natriuretic peptide (CNP) is the major natriuretic peptide in human cerebrospinal fluid. Brain research 69 8330189
2010 Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women. Obesity (Silver Spring, Md.) 68 20966902
2009 NG2 cell response in the CNP-EGFP mouse after contusive spinal cord injury. Glia 68 18756526
1995 Shear stress induces expression of CNP gene in human endothelial cells. FEBS letters 68 7589445
1998 Four-kilobase sequence of the mouse CNP gene directs spatial and temporal expression of lacZ in transgenic mice. Journal of neuroscience research 67 9710259
2007 A cluster of translocation breakpoints in 2q37 is associated with overexpression of NPPC in patients with a similar overgrowth phenotype. Human mutation 66 17676597
2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature 66 15815621
2015 The Local CNP/GC-B system in growth plate is responsible for physiological endochondral bone growth. Scientific reports 64 26014585
1994 Molecular cloning and chromosomal assignment of the mouse C-type natriuretic peptide (CNP) gene (Nppc): comparison with the human CNP gene (NPPC). Genomics 63 7698765
2009 C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 62 19805384
2005 Amino-terminal proCNP: a putative marker of cartilage activity in postnatal growth. Pediatric research 60 16006435
2018 Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 59 29987050
2010 Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. Journal of psychiatric research 59 20398908
2017 Mutations in C-natriuretic peptide (NPPC): a novel cause of autosomal dominant short stature. Genetics in medicine : official journal of the American College of Medical Genetics 57 28661490
1994 C-type natriuretic peptide (CNP) in the pituitary: is CNP an autocrine regulator of gonadotropes? Endocrinology 54 7988473
2005 Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain. Alcoholism, clinical and experimental research 50 16205370
2019 TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias. The Journal of pharmacology and experimental therapeutics 49 31235532
2020 Nanosilk Increases the Strength of Diabetic Skin and Delivers CNP-miR146a to Improve Wound Healing. Frontiers in immunology 46 33193424
2010 Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias. Endocrine journal 44 20567091
2012 NPPC/NPR2 signaling is essential for oocyte meiotic arrest and cumulus oophorus formation during follicular development in the mouse ovary. Reproduction (Cambridge, England) 43 22696190
2007 Mammalian 2',3' cyclic nucleotide phosphodiesterase (CNP) can function as a tRNA splicing enzyme in vivo. RNA (New York, N.Y.) 43 18094118
2017 Natriuretic peptide receptor 2 (NPR2) localized in bovine oocyte underlies a unique mechanism for C-type natriuretic peptide (CNP)-induced meiotic arrest. Theriogenology 39 29080478
2024 CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis. Circulation research 38 38456298
2014 In aging, the vulnerability of rat brain mitochondria is enhanced due to reduced level of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNP) and subsequently increased permeability transition in brain mitochondria in old animals. Neurochemistry international 38 25277077
2021 Mechanism of quercetin on the improvement of ovulation disorder and regulation of ovarian CNP/NPR2 in PCOS model rats. Journal of the Formosan Medical Association = Taiwan yi zhi 37 34538551
2020 Exosomal 2',3'-CNP from mesenchymal stem cells promotes hippocampus CA1 neurogenesis/neuritogenesis and contributes to rescue of cognition/learning deficiencies of damaged brain. Stem cells translational medicine 36 31943851
2016 Transient Cnp expression by early progenitors causes Cre-Lox-based reporter lines to map profoundly different fates. Glia 36 27807896
2007 CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis. Biochemical and biophysical research communications 35 17336931
2007 ProCNP and CNP are expressed primarily in male genital organs. Regulatory peptides 35 17928074
1999 Cloning, characterization, and functional expression of a CNP receptor regulating CFTR in the shark rectal gland. The American journal of physiology 34 9950772
2020 Characterization of a nitric oxide (NO) donor molecule and cerium oxide nanoparticle (CNP) interactions and their synergistic antimicrobial potential for biomedical applications. Journal of colloid and interface science 33 33187669
2021 Circ-AFF2/miR-650/CNP axis promotes proliferation, inflammatory response, migration, and invasion of rheumatoid arthritis synovial fibroblasts. Journal of orthopaedic surgery and research 32 33653372
2004 Four natriuretic peptides (ANP, BNP, VNP and CNP) coexist in the sturgeon: identification of BNP in fish lineage. Journal of molecular endocrinology 32 15072558
2013 Genotype-Phenotype Correlation of 2q37 Deletions Including NPPC Gene Associated with Skeletal Malformations. PloS one 30 23805197
2010 Cuprizone-induced demyelination in CNP::GFP transgenic mice. The Journal of comparative neurology 30 20437527
2002 CNP production in the kidney and effects of protein intake restriction in nephrotic syndrome. American journal of physiology. Renal physiology 29 12167597
1999 Shear stress induction of C-type natriuretic peptide (CNP) in endothelial cells is independent of NO autocrine signaling. Annals of biomedical engineering 29 10468226
1994 Generation of a monoclonal antibody against the myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase) suitable for biochemical and for immunohistochemical investigations of CNP. Neurochemical research 25 7877717
2019 Effects of Sprifermin, IGF1, IGF2, BMP7, or CNP on Bovine Chondrocytes in Monolayer and 3D Culture. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 24 31608492
2013 SERCA2 activity is involved in the CNP-mediated functional responses in failing rat myocardium. British journal of pharmacology 24 23808942
2005 Comparative analysis of the natriuretic peptide precursor gene cluster in vertebrates reveals loss of ANF and retention of CNP-3 in chicken. Developmental dynamics : an official publication of the American Association of Anatomists 24 15895405
2000 C-type natriuretic peptide (CNP) effects in anterior pituitary cell lines: evidence for homologous desensitisation of CNP-stimulated cGMP accumulation in alpha T3-1 gonadotroph-derived cells. The Journal of endocrinology 24 10856898
1999 Action of C-type natriuretic peptide (CNP) on passive avoidance learning in rats: involvement of transmitters. The European journal of neuroscience 24 10510194
2014 Epidermal growth factor-network signaling mediates luteinizing hormone regulation of BNP and CNP and their receptor NPR2 during porcine oocyte meiotic resumption. Molecular reproduction and development 23 25348585
2008 Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification. Biochemical and biophysical research communications 23 18775416
2022 CNP regulates cardiac contractility and increases cGMP near both SERCA and TnI: difference from BNP visualized by targeted cGMP biosensors. Cardiovascular research 22 33970224
2021 The mRNA-destabilizing protein Tristetraprolin targets "meiosis arrester" Nppc mRNA in mammalian preovulatory follicles. Proceedings of the National Academy of Sciences of the United States of America 22 34031239
2013 CNP and DPYSL2 mRNA expression and promoter methylation levels in brain of Alzheimer's disease patients. Journal of Alzheimer's disease : JAD 22 22954668
2007 A single nucleotide mutation in Nppc is associated with a long bone abnormality in lbab mice. BMC genetics 22 17439653
2021 Changes in soil total, microbial and enzymatic C-N-P contents and stoichiometry with depth and latitude in forest ecosystems. The Science of the total environment 21 34785225
2020 CNP mediated selective toxicity on melanoma cells is accompanied by mitochondrial dysfunction. PloS one 21 31951630
2018 Biodegradation of 2,6-dibromo-4-nitrophenol by Cupriavidus sp. strain CNP-8: Kinetics, pathway, genetic and biochemical characterization. Journal of hazardous materials 21 30176407
2006 CNP, but not ANP or BNP, relax human isolated subcutaneous resistance arteries by an action involving cyclic GMP and BKCa channels. Journal of the renin-angiotensin-aldosterone system : JRAAS 21 17083062
2003 Ambient salinity-dependent effects of homologous natriuretic peptides (ANP, VNP, and CNP) on plasma cortisol level in the eel. General and comparative endocrinology 21 12606274
2000 Effects of natriuretic peptides (ANP, BNP, CNP) on catecholamine synthesis and TH mRNA levels in PC12 cells. Life sciences 21 10834306
2022 CNP, the Third Natriuretic Peptide: Its Biology and Significance to the Cardiovascular System. Biology 20 36101368
2020 Can extracellular vesicles from bovine ovarian follicular fluid modulate the in-vitro oocyte meiosis progression similarly to the CNP-NPR2 system? Theriogenology 20 32814248
2010 Circulating C-type natriuretic peptide (CNP) rescues chondrodysplastic CNP knockout mice from their impaired skeletal growth and early death. Endocrinology 20 20610569
2000 Critical evaluation of p-nitrophenylphosphorylcholine (p-NPPC) as artificial substrate for the detection of phospholipase C*. Enzyme and microbial technology 20 10713220
1997 In vivo activation of CFTR-dependent chloride transport in murine airway epithelium by CNP. The American journal of physiology 20 9374736
1995 Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus. Journal of neuroimmunology 20 7706429
2019 Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 31090455
2004 Presence of C-type natriuretic peptide (CNP) in guinea pig caecum: role and mechanisms of CNP in circular smooth muscle relaxation. Neurogastroenterology and motility 19 15198660
2015 CNP signal pathway up-regulated in rectum of depressed rats and the interventional effect of Xiaoyaosan. World journal of gastroenterology 18 25663771
2011 Central and peripheral forms of C-type natriuretic peptide (CNP): evidence for differential regulation in plasma and cerebrospinal fluid. Peptides 18 21262296
1996 Binding of CNP-22 and CNP-53 to cultured mouse astrocytes and effects on cyclic GMP. Peptides 18 8822517
2022 Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP. British journal of clinical pharmacology 17 35481707
2021 Lung function improves after delayed treatment with CNP-miR146a following acute lung injury. Nanomedicine : nanotechnology, biology, and medicine 17 34838994
2018 Biodegradation of 2-chloro-4-nitrophenol via a hydroxyquinol pathway by a Gram-negative bacterium, Cupriavidus sp. strain CNP-8. AMB Express 17 29560541
2018 The cyclic phosphodiesterase CNP and RNA cyclase RtcA fine-tune noncanonical XBP1 splicing during ER stress. The Journal of biological chemistry 17 30355738
2017 Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia. Journal of dental research 17 28644737
2008 Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab -/- mice. Peptides 17 18554750
1985 An immunochemical investigation of 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in bovine cerebrum and human oligodendroglioma. Journal of neuroscience research 17 2580990
2023 CNP-miR146a improves outcomes in a two-hit acute- and ventilator-induced lung injury model. Nanomedicine : nanotechnology, biology, and medicine 16 37116556
2013 Neutral endopeptidase (CD10) is abundantly expressed in the epididymis and localized to a distinct population of epithelial cells--its relevance for CNP degradation. Molecular and cellular endocrinology 16 24099862
2006 A novel peptide from the ACEI/BPP-CNP precursor in the venom of Crotalus durissus collilineatus. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 16 16979945
2023 CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2. Circulation research 15 36715019
2003 Role of calcium-activated potassium currents in CNP-induced relaxation of gastric antral circular smooth muscle in guinea pigs. World journal of gastroenterology 15 12970905
1999 C-type natriuretic peptide (CNP) effects on intracellular calcium [Ca2+]i in mouse gonadotrope-derived alphaT3-1 cell line. Regulatory peptides 15 10535407
1997 Synthesis of C-type natriuretic peptide (CNP) by immortalized LHRH cells. Journal of neuroendocrinology 15 9089468
2018 C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis and inflammation in non-alcoholic steatohepatitis. Life sciences 14 30114411
2006 Identification of a natriuretic peptide (NP) in cyclostomes (lamprey and hagfish): CNP-4 is the ancestral gene of the NP family. General and comparative endocrinology 14 16740263
2004 Effect of C-type natriuretic peptide (CNP) on water channel aquaporin-4 (AQP4) expression in cultured astrocytes. Brain research. Molecular brain research 14 15010203
1994 In vivo phosphorylation of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP): CNP in brain myelin is phosphorylated by forskolin- and phorbol ester-sensitive protein kinases. Neurochemical research 14 8065530
2023 Biochar amendments combined with organic fertilizer improve maize productivity and mitigate nutrient loss by regulating the C-N-P stoichiometry of soil, microbiome, and enzymes. Chemosphere 13 36870619
2005 C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo. Cardiovascular research 13 15914122
1997 Detection of C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP-B) receptor mRNAs in rat inner ear. Neuroreport 13 9080425
1994 The myelin protein CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase): immunoaffinity purification of CNP from pig and rat brain using a monoclonal antibody and phosphorylation of CNP by cyclic nucleotide-dependent protein kinases. Biological chemistry Hoppe-Seyler 13 8011177
2022 Sequential IVM by CNP preincubation and cooperating of PGE2 with AREG enhances developmental competence of SCNT reconstructs in goat. Scientific reports 12 35273320
2019 Electroacupuncture promotes the gastrointestinal motility of diabetic mice by CNP/NPR-B-cGMP and PDE3A-cGMP signaling. Neurogastroenterology and motility 12 30672071
2012 CNP-1 (ARRD-17), a novel substrate of calcineurin, is critical for modulation of egg-laying and locomotion in response to food and lysine sensation in Caenorhabditis elegans. Journal of molecular biology 12 22300764