Affinage

PTN

Pleiotrophin · UniProt P21246

Length
168 aa
Mass
18.9 kDa
Annotated
2026-06-10
78 papers in source corpus 25 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTN (pleiotrophin/HBNF/HBGF-8) is a secreted heparin-binding growth factor that signals through receptor protein tyrosine phosphatases and proteoglycan co-receptors to regulate neuronal maturation, glial differentiation, stem cell behavior, and tissue remodeling (PMID:2610682, PMID:2049182, PMID:30667096). First purified as a 17 kDa heparin-binding mitogen from bovine uterus and as a neurotrophic factor from bovine brain (PMID:2610682, PMID:2049182), PTN binds sulfated glycosaminoglycans and forms non-covalent dimers whose assembly depends on cellular sulfation (PMID:10600521). Its central signaling logic is the inactivation of the receptor phosphatase RPTPβ/ζ (PTPRZ1): PTN binding blocks phosphatase activity, allowing accumulation of phosphotyrosine on downstream substrates, including the activation domain of ALK (ligand-independent kinase activation) and AFAP1L2, whose phosphorylation drives PI3K-AKT-mTOR signaling and oligodendrocyte precursor differentiation (PMID:23777859, PMID:30667096). Through PTPRZ1/ALK-AKT signaling, astrocyte- and neural stem cell-derived PTN promotes hippocampal neurogenesis, dendritic development of newborn neurons, and cognition (PMID:30497772, PMID:39729991), while dysregulated PTN release from quiescent neural stem cells produces aberrant neurogenesis and manic-like behavior (PMID:40069581). PTN also engages syndecan co-receptors in non-neural contexts, activating SDC2 to sustain spermatogonial stem cell proliferation and SDC4 to drive cardiac fibroblast proliferation and macrophage inflammation in pressure-overload cardiomyopathy (PMID:39285301, PMID:39765325), and acts through PTPRZ1 to promote osteogenic differentiation (PMID:40149671). PTN expression is transcriptionally controlled in a context-specific manner—by AP-1/JUN in fibroblasts, by IFN-γ/JAK/STAT1 in macrophages, and by progesterone/cAMP/PKA/C/EBPβ in uterine stromal cells (PMID:15840658, PMID:19917672, PMID:28657144)—and its regulated secretion from oligodendrocyte precursors requires the TRAPPC12-Mea6/cTAGE5-COPII trafficking machinery (PMID:38439956).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1989 High

    Established PTN as a discrete secreted growth factor by purifying it as a heparin-binding mitogen, answering whether the activity was a defined protein.

    Evidence Heparin-Sepharose/cation exchange purification and N-terminal sequencing from bovine uterus with 3H-thymidine mitogenic assay in NIH 3T3 cells

    PMID:2610682

    Open questions at the time
    • No receptor or signaling mechanism identified
    • Physiological source and target tissue unresolved
  2. 1991 High

    Showed the same heparin-binding protein has neurotrophic activity, extending PTN function beyond fibroblast mitogenesis and documenting proteolytic C-terminal truncation.

    Evidence Purification from bovine brain, amino acid sequencing, SDS-PAGE, neurotrophic assay on perinatal rat neurons

    PMID:2049182

    Open questions at the time
    • Functional significance of truncated forms unknown
    • No receptor identified
  3. 1993 Medium

    Defined the human gene structure and alternative splicing, establishing PTN protein heterogeneity at the genomic level.

    Evidence Genomic library screening, Southern blotting, cDNA sequencing, protein characterization from bovine brain

    PMID:8484754

    Open questions at the time
    • Functional difference between splice variants not tested
  4. 1999 Medium

    Resolved the biophysical basis of signaling competence by showing PTN dimerizes in a sulfation-dependent manner.

    Evidence DSS cross-linking, heparin-Sepharose chromatography, chlorate sulfation inhibition, conditioned medium analysis of NIH-3T3 cells

    PMID:10600521

    Open questions at the time
    • Link between dimerization state and receptor activation not directly shown
    • Structural model of the dimer absent
  5. 2000 High

    Identified an endogenous retroviral promoter as a context-specific driver of PTN expression in trophoblast/choriocarcinoma cells via an Sp1 element.

    Evidence In situ hybridization, promoter deletion assays, EMSA/supershift, site-directed mutagenesis, Sp1 overexpression in Drosophila SL2 cells

    PMID:10962555

    Open questions at the time
    • Relevance to non-trophoblast tissue regulation unclear
  6. 2005 Medium

    Placed PTN downstream of AP-1/JUN in fibroblasts and demonstrated a paracrine mitogenic role on keratinocytes during wound healing.

    Evidence Expression profiling of Jun-/- MEFs, RT-PCR, in situ hybridization, feeder-layer keratinocyte co-culture, in vivo wound model

    PMID:15840658

    Open questions at the time
    • Receptor mediating keratinocyte response not identified
    • Direct JUN binding to PTN promoter not shown
  7. 2009 High

    Defined IFN-γ/JAK/STAT1 as an inducible transcriptional input to PTN in macrophages, mapping a functional GAS element in the promoter.

    Evidence JAK inhibitors, STAT1 phosphorylation assays, promoter deletion, EMSA/supershift, ChIP, siRNA of STAT1/STAT3/p42

    PMID:19917672

    Open questions at the time
    • Downstream consequence of macrophage PTN secretion not addressed
  8. 2010 Medium

    Connected PTN/RPTPβ/ζ signaling to cancer cell migration through integrin αvβ3, FAK, PI3K, and ERK, and identified menin as a transcriptional repressor.

    Evidence Menin overexpression, RT-PCR, migration assays, pathway inhibitors, integrin blocking in A549 cells

    PMID:20639902

    Open questions at the time
    • Direct menin binding to the PTN locus not shown
    • Order of integrin/FAK/PI3K events unresolved
  9. 2013 Medium

    Articulated the core mechanistic model: PTN inactivates RPTPβ/ζ phosphatase, enabling ligand-independent ALK autophosphorylation and broad downstream tyrosine phosphorylation.

    Evidence Mechanistic synthesis of phosphatase activity and tyrosine phosphorylation studies (review)

    PMID:23777859

    Open questions at the time
    • Review synthesis rather than primary data in this entry
    • Stoichiometry of receptor inactivation not quantified
  10. 2012 Medium

    Defined PTN as a negative regulator of mammary epithelial expansion and ductal outgrowth acting via cell-matrix adhesion and ERK suppression, distinguishing motility from proliferation roles.

    Evidence Anti-PTN blocking antibody, RTCA impedance, 3D mammosphere assay, in vivo mammary analysis, phospho-ERK Western blot

    PMID:23077670

    Open questions at the time
    • Receptor mediating mammary effects not identified
    • Mechanism of adhesion disruption unresolved
  11. 2014 Medium

    Established PTN/PTPRZ1 as a survival signal in ovarian cancer acting through MAPK effectors.

    Evidence siRNA knockdown of PTN/PTPRZ1, apoptosis assays, ELISA, survival-gene expression profiling

    PMID:25418856

    Open questions at the time
    • Direct MAPK activation mechanism downstream of PTPRZ1 not delineated
  12. 2014 Medium

    Placed PTN as a required intermediary in CART neuropeptide-driven neurite outgrowth after ischemic stress.

    Evidence siRNA PTN knockdown, GAP43 Western blot, post-OGD CART treatment in cortical neurons

    PMID:25010400

    Open questions at the time
    • Receptor coupling CART to PTN expression unknown
  13. 2017 Medium

    Integrated PTN into hormonal control of uterine decidualization, acting downstream of progesterone/cAMP/PKA/C/EBPβ to regulate Hand2 and decidual markers.

    Evidence siRNA of PTN/C/EBPβ, constitutive PTN activation, PKA inhibitor, RT-PCR of decidualization markers in uterine stromal cells

    PMID:28657144

    Open questions at the time
    • Receptor mediating decidual PTN effects not identified
  14. 2018 High

    Demonstrated in vivo that neural stem cell-derived PTN is a feedforward signal required for proper dendritic development of newborn neurons.

    Evidence Cell ablation, retroviral single-cell labeling, signaling modulation, morphological analysis in adult hippocampus

    PMID:30497772

    Open questions at the time
    • Receptor on newborn neurons not pinned down in this study
  15. 2018 Medium

    Linked chemotherapy-induced PTN/PTPRZ1 upregulation, via CDKN1A, to NF-κB-driven chemoresistance in triple-negative breast cancer.

    Evidence Microarray, CCK-8/colony/apoptosis assays, siRNA of PTPRZ1, pathway inhibition in TNBC cells

    PMID:30497491

    Open questions at the time
    • Direct CDKN1A control of PTN transcription not shown
  16. 2019 High

    Provided the most direct substrate-level mechanism: PTN-PTPRZ signaling drives AFAP1L2 tyrosine phosphorylation and PI3K-AKT-mTOR activation to promote oligodendrocyte differentiation and remyelination.

    Evidence Phosphoproteomics, in vitro PTPRZ phosphatase assay, HEK293T overexpression, AFAP1L2 siRNA, PI3K inhibition, catalytically inactive PTPRZ knock-in mice, cuprizone model

    PMID:30667096

    Open questions at the time
    • Whether AFAP1L2 is a direct or indirect PTPRZ substrate in vivo not fully resolved
  17. 2021 Medium

    Showed tumor-cell-derived PTN promotes neurite outgrowth, implicating PTN in cancer-associated neural remodeling.

    Evidence shRNA knockdown in BxPC-3 pancreatic cancer cells, DRG co-culture neurite assay

    PMID:21677838

    Open questions at the time
    • Neuronal receptor mediating outgrowth not identified
  18. 2024 Medium

    Identified syndecan co-receptors as alternative PTN effectors: SDC2 sustains spermatogonial stem cell self-renewal and SDC4 drives cardiac fibroblast/macrophage inflammatory responses.

    Evidence Co-IP, knockdown with PTN rescue in SSCs; scRNA-seq/CellChat plus in vitro and TAC in vivo validation for SDC4

    PMID:39285301 PMID:39765325

    Open questions at the time
    • Whether syndecans act independently or as PTPRZ1 co-receptors not resolved
    • Structural basis of PTN-syndecan binding unknown
  19. 2024 High

    Extended the PTPRZ1/ALK-AKT axis in vivo to astrocyte-derived PTN regulation of hippocampal neurogenesis and cognition under demyelination.

    Evidence Astrocyte-specific conditional PTN knockout and overexpression, AKT analysis, neurogenesis and behavioral testing in demyelination model

    PMID:39729991

    Open questions at the time
    • Relative contribution of PTPRZ1 versus ALK not dissected
  20. 2024 High

    Defined the secretory route for PTN, showing TRAPPC12-Mea6/cTAGE5-COPII machinery is required for PTN release from oligodendrocyte precursors.

    Evidence Co-IP of TRAPPC12-Mea6, Mea6 conditional knockout, COPII component analysis, secretion assay, exogenous PTN rescue

    PMID:38439956

    Open questions at the time
    • Whether this trafficking route is PTN-specific or general unresolved
  21. 2024 Medium

    Linked PTN-PTPRZ1 signaling to bone formation through PLCG1 phosphorylation, NCOA3 nuclear translocation, and ROS reduction promoting osteogenic differentiation.

    Evidence Phosphoproteomics, immunofluorescence, ALP/TUNEL assays, RNA-seq, in vivo osteoporotic fracture healing

    PMID:40149671

    Open questions at the time
    • Direct PTPRZ1 dependence of PLCG1 phosphorylation not formally shown
  22. 2025 Medium

    Implicated dysregulated quiescent neural stem cell PTN release in manic-like behavior, identifying excess PTN as a disease-relevant driver of aberrant neurogenesis.

    Evidence scRNA-seq, pharmacological and molecular PTN inhibition, behavioral and neurogenesis analysis in Shank3-overexpressing mice

    PMID:40069581

    Open questions at the time
    • Receptor pathway downstream of excess PTN not defined here
  23. 2025 Low

    Proposed a non-receptor-phosphatase mechanism in which PTN binds SIRT1 to activate the AMPK-PGC1α axis and protect cardiomyocytes from oxidative stress.

    Evidence PTN-SIRT1 binding assay, AMPK Thr172/PGC1α Western blot, PTN overexpression, ROS/apoptosis flow cytometry, in vivo cardiotoxicity model

    PMID:41640280

    Open questions at the time
    • Methods limited in detail and single publication
    • Direct PTN-SIRT1 binding not independently confirmed
    • Reconciliation with secreted-ligand biology unclear
  24. 2025 Medium

    Connected stromal androgen receptor signaling to PTN as an extrinsic regulator of epithelial ferroptosis via MUFA phospholipid biosynthesis and GPX4.

    Evidence Genetically engineered mice, human organotypic cultures, ferroptosis and castration models (preprint)

    Open questions at the time
    • Preprint not peer-reviewed
    • Receptor mediating epithelial PTN response not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PTN partitions signaling among PTPRZ1, ALK, and syndecan co-receptors across cell types, and the structural basis of dimer/glycosaminoglycan-dependent receptor selection, remains unresolved.
  • No structure of a PTN-receptor complex in the corpus
  • Rules governing receptor choice across tissues unknown
  • Quantitative contribution of dimerization to signaling not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
AFAP1L2ALKPTPRZ1SDC2SDC4SIRT1TRAPPC12

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 PTN (HBGF-8) was purified to near homogeneity from bovine uterus as a novel 17 kDa heparin-binding growth factor that binds tightly to cation exchange resins and heparin-Sepharose, and stimulates DNA synthesis (3H-thymidine incorporation) in NIH 3T3 fibroblasts with mitogenic activity comparable to aFGF. Protein purification (heparin-Sepharose affinity chromatography, cation exchange), N-terminal amino acid sequencing, mitogenic assay (3H-thymidine incorporation in NIH 3T3 cells) Biochemical and biophysical research communications High 2610682
1991 PTN (HBNF) was purified to homogeneity from bovine brain and found to have neurotrophic activity for perinatal rat neurons; C-terminally truncated forms (lacking ~14 or ~22 residues) are generated by proteolysis during extraction, comprising major products in the absence of protease inhibitors. Protein purification (pH 4.5 extraction, ammonium sulfate precipitation, cation exchange, heparin-Sepharose, reverse-phase HPLC), amino acid sequencing, SDS-PAGE Growth factors (Chur, Switzerland) High 2049182
1992 Recombinant PTN (HBNF) inhibits infectivity of herpes simplex viruses types 1 and 2 and human cytomegalovirus; carboxymethylated HBNF (which retains heparin-binding but not free basic charge) loses antiviral activity, suggesting the mechanism involves competition for cell-surface heparan sulfate proteoglycan binding. In vitro antiviral infectivity assay with recombinant HBNF and carboxymethylated HBNF variant Biochemical and biophysical research communications Medium 1335242
1993 The human PTN (HBNF) gene spans at least 42 kb and is organized in 5 exons; alternative splicing at the exon 5 acceptor site generates a variant mRNA with a 3-bp deletion, encoding a protein (des-Ala119-HBNF) lacking one alanine residue, which comprises ~20% of total HBNF protein in bovine brain. Southern blotting, genomic library screening, cDNA sequencing, protein characterization from bovine brain Biochemical and biophysical research communications Medium 8484754
1999 PTN (HARP) forms non-covalent dimers, and dimerization is promoted by heparin and other sulfated glycosaminoglycans (dermatan sulfate, chondroitin sulfate-C); chlorate treatment of cells (which inhibits sulfation) blocks dimer formation; PTN is secreted as a dimer in conditioned medium of NIH-3T3 cells overexpressing PTN. DSS cross-linking, heparin-Sepharose affinity chromatography, chlorate treatment, conditioned medium analysis Biochemical and biophysical research communications Medium 10600521
2000 A human endogenous retrovirus-like element (HERV-E.PTN) inserted into the PTN gene generates a novel promoter driving PTN expression in choriocarcinoma and trophoblast cells; a Sp1-binding site within the retroviral enhancer (+443 to +486) is essential for this promoter activity, as shown by site-specific mutation abolishing activity and Sp1 overexpression in Drosophila SL2 cells confirming Sp1-dependent activation. In situ hybridization, transient transfection promoter assays, deletion analysis, EMSA/supershift, site-directed mutagenesis, Sp1 overexpression in SL2 cells Oncogene High 10962555
2005 PTN and SDF-1 expression in dermal fibroblasts is regulated by the AP-1 transcription factor JUN; fibroblast-secreted PTN exerts a mitogenic (proliferative) effect on primary human keratinocytes in a heterologous feeder layer co-culture system; PTN expression is upregulated during cutaneous wound healing in vivo. Gene expression profiling of Jun-/- vs wild-type MEFs, semi-quantitative RT-PCR, in situ hybridization on skin sections, heterologous feeder layer co-culture keratinocyte proliferation assay, in vivo wound healing model Journal of cell science Medium 15840658
2009 IFN-γ markedly induces PTN mRNA expression in macrophages through the JAK/STAT1 signaling pathway; a gamma-activated sequence (GAS) at -2086 to -2078 bp in the PTN promoter is essential for IFN-γ-regulated promoter activity; STAT1 (but not STAT3 or p42) is required for PTN expression, as shown by siRNA knockdown; STAT1 and STAT3 bind to the GAS element at the chromatin level. JAK inhibitor treatment (WHI-P154, ATA), STAT1 phosphorylation assays, PTN promoter deletion analysis, EMSA, supershift assay, ChIP, siRNA knockdown of STAT1/STAT3/p42 FASEB journal High 19917672
2010 Menin represses PTN transcription and indirectly reduces RPTP β/ζ expression; PTN/RPTP β/ζ signaling promotes A549 lung cancer cell migration in conjunction with integrin αvβ3, focal adhesion kinase (FAK), PI3K, and phosphorylated ERK1/2; ectopic menin expression significantly represses PTN-mediated cell migration. Ectopic menin overexpression, RT-PCR for PTN and RPTP β/ζ, cell migration assay, pathway inhibitor studies (PI3K inhibitor, ERK inhibitor), integrin αvβ3 blocking Oncogene Medium 20639902
2012 Endogenous PTN in mammary epithelial cells (MECs) promotes motility and invasion (but not proliferation) as demonstrated by anti-PTN blocking antibody; PTN inhibits expansion and differentiation of epithelial progenitor cells by disrupting cell-matrix adhesion; in vivo, PTN inhibits ductal outgrowth and branching via inhibition of phospho-ERK1/2 signaling in mammary epithelial cells. Anti-PTN blocking antibody treatment, real-time impedance monitoring (RTCA), 3D culture mammosphere assay, in vivo mammary gland analysis, Western blotting for phospho-ERK1/2 PloS one Medium 23077670
2013 PTN activates anaplastic lymphoma kinase (ALK) via 'Ligand Independent Activation': PTN binds and inactivates the phosphatase activity of its receptor RPTPβ/ζ; inactivated RPTPβ/ζ can no longer dephosphorylate phosphotyrosine sites in the ALK activation domain, resulting in ALK autophosphorylation and autoactivation; this PTN/RPTPβ/ζ pathway also coordinately regulates tyrosine phosphorylation of other downstream proteins. Review/mechanistic synthesis of experimental findings (phosphatase activity assays, tyrosine phosphorylation studies of ALK cited in reviewed papers) Biochimica et biophysica acta Medium 23777859
2014 PTN is expressed, produced, and secreted by epithelial ovarian cancer (EOC) cells; siRNA-mediated knockdown of PTN or its receptor PTPRZ1 induces significant apoptosis; PTN signaling in EOC cells activates MAPK family members as downstream effectors, as identified by expression profiling of 36 survival-related genes after PTN knockdown. siRNA knockdown, Western blot, ELISA, cell viability assay, expression profiling of 36 survival genes, computational pathway mapping Molecular carcinogenesis Medium 25418856
2017 In uterine stromal cells, progesterone stimulates PTN expression via cAMP/PKA/C/EBPβ pathway; PTN acts downstream of C/EBPβ to promote decidualization marker expression (Prl8a2, Prl3c1); PTN mediates C/EBPβ regulation of Hand2, a downstream target in uterine stromal cell differentiation. siRNA knockdown of PTN and C/EBPβ, constitutive PTN activation, PKA inhibitor (H89) treatment, RT-PCR for decidualization markers, progesterone/cAMP treatment of uterine stromal cells Journal of cellular physiology Medium 28657144
2018 Adult hippocampal neural stem cells (NSCs) continuously supply PTN as a feedforward signal to newborn neurons; ablation of NSCs or loss of PTN signaling causes defective dendritic development and arborization in newborn neurons. Cell ablation, retrovirus-mediated single-cell labeling, signaling pathway modulation, morphological analysis of newborn neurons Neuron High 30497772
2018 Chemotherapy (in TNBC cells) drives upregulation of PTN and PTPRZ1 expression via CDKN1A; elevated PTN/PTPRZ1 promotes chemoresistance by activating the NF-κB pathway, enhancing tumor proliferation and inhibiting apoptosis; siRNA knockdown of PTPRZ1 revealed its role in this pathway. Microarray analysis, CCK-8 assay, colony formation, apoptosis analysis, siRNA knockdown, pathway inhibition Cell communication and signaling Medium 30497491
2019 PTN-PTPRZ signaling promotes oligodendrocyte precursor cell (OPC) differentiation by enhancing tyrosine phosphorylation of AFAP1L2; PTPRZ dephosphorylates AFAP1L2 at tyrosine residues in vitro and in HEK293T cells; PTN-induced AFAP1L2 phosphorylation activates the PI3K-AKT-mTOR pathway; knock-in mice with catalytically inactive PTPRZ (Cys-to-Ser mutation) show enhanced OPC differentiation and earlier remyelination. Phosphoproteomics in OPC-like OL1 cells, in vitro PTPRZ phosphatase assay, HEK293T overexpression, siRNA knockdown of AFAP1L2, PI3K inhibitor treatment, Cys-to-Ser knock-in mice, cuprizone demyelination model Glia High 30667096
2021 PTN promotes neurite outgrowth from dorsal root ganglion (DRG) neurons; shRNA-mediated knockdown of PTN in pancreatic cancer BxPC-3 cells reduces PTN expression and inhibits neurite outgrowth from co-cultured DRG neurons. Adenovirus-mediated shRNA knockdown, RT-PCR, immunocytochemistry, Western blot, DRG co-culture neurite morphology assay World journal of gastroenterology Medium 21677838
2024 PTN secreted by Leydig cells activates syndecan-2 (SDC2) on spermatogonial stem cells (SSCs); SDC2 knockdown impairs SSC proliferation, DNA synthesis, PLZF expression, and downregulates GFRA1 and HIF-1 signaling; exogenous PTN rescues proliferation and GFRA1 expression in SDC2 knockdown SSC lines; protein immunoprecipitation confirmed the PTN-SDC2 interaction. Single-cell sequencing data analysis, immunofluorescence, STRING prediction, protein immunoprecipitation, SDC2 knockdown, transcriptome analysis, exogenous PTN rescue experiment Biological research Medium 39285301
2024 Astrocyte-derived PTN promotes hippocampal neurogenesis and cognition by signaling through PTPRZ1 or ALK receptors to activate AKT signaling; conditional deletion of PTN in astrocytes exacerbates neurogenic deficits in demyelinated hippocampus; PTN overexpression in astrocytes reverses neurogenic and cognitive impairments caused by demyelination. Conditional knockout (astrocyte-specific PTN deletion), PTN overexpression, AKT signaling pathway analysis, neurogenesis assays, behavioral cognitive testing, demyelination model Stem cell reports High 39729991
2024 PTN binds to PTPRZ1 receptor on rat bone marrow mesenchymal stem cells (rBMSCs), induces PLCG1 phosphorylation and NCOA3 nuclear translocation, reduces cellular reactive oxygen species (ROS), and thereby promotes osteogenic differentiation and inhibits apoptosis; PTN promotes fracture healing in osteoporotic animals in vivo. Phosphorylation quantitative proteomics, immunofluorescence, ALP detection, TUNEL assay, RNA sequencing, in vivo fracture healing in osteoporosis rats Biomedicines Medium 40149671
2024 TRAPPC12 interacts with Mea6/cTAGE5 and together they regulate PTN secretion from oligodendrocyte precursor cells (OPCs); Mea6/cTAGE5 ablation disrupts COPII trafficking components (SEC13, SEC31A, SAR1) and impairs PTN secretion; exogenous PTN supplementation rescues OPC differentiation deficits caused by Mea6 deficiency. Co-immunoprecipitation (TRAPPC12-Mea6 interaction), conditional knockout (Mea6 cKO in OPCs), COPII component localization/expression analysis, PTN secretion assay, exogenous PTN rescue experiment iScience High 38439956
2025 PTN secreted by cardiac fibroblasts promotes fibroblast self-proliferation/invasion and stimulates macrophage inflammatory responses (TNF-α, IL-6, Cox-2) through binding to syndecan-4 (SDC4) receptor, contributing to pressure overload-induced hypertrophic cardiomyopathy. Single-cell RNA-seq analysis (scRNA-seq), CellChat cell-cell interaction analysis, in vitro validation (RT-qPCR, EdU staining, transwell assay), in vivo TAC mouse model (Western blot, immunofluorescence, echocardiography) Life sciences Medium 39765325
2025 Excessive PTN released by dysregulated quiescent neural stem cells (qNSCs) contributes to manic-like phenotypes in Shank3-overexpressing mice; pharmacological and molecular inhibition of PTN in qNSCs rescues aberrant neurogenesis and alleviates manic-like social deficits. Single-cell RNA sequencing (scRNA-seq), pharmacological PTN inhibition, molecular knockdown of PTN in qNSCs, behavioral assays, neurogenesis analysis Nature communications Medium 40069581
2025 PTN directly binds to SIRT1 and activates AMPK phosphorylation at Thr172, triggering the AMPK-PGC1α axis to reprogram mitochondrial energy metabolism; PTN overexpression reduces mitochondrial oxidative stress and apoptosis in cardiomyocytes treated with doxorubicin. PTN-SIRT1 binding assay, Western blot for AMPK phosphorylation (Thr172) and PGC1α, PTN overexpression, flow cytometry for ROS/apoptosis, in vivo cardiotoxicity model Acta biochimica et biophysica Sinica Low 41640280
2025 Androgen receptor (AR) signaling in prostate stroma controls a PTN-mediated extrinsic signaling pathway that regulates monounsaturated fatty acid (MUFA) phospholipid biosynthesis and GPX4 expression to suppress prostate epithelial ferroptosis after castration. In vivo analyses in genetically-engineered mice, human organotypic cultures, ferroptosis assays, castration model bioRxivpreprint Medium
2014 CART (cocaine- and amphetamine-regulated transcript) neuropeptide facilitates neurite outgrowth in cortical neurons after oxygen-glucose deprivation through a PTN-dependent pathway; siRNA-mediated PTN knockdown abolishes the CART-stimulated increase in GAP43 protein levels. siRNA knockdown of PTN, Western blot for GAP43, post-OGD CART treatment, primary mouse cortical neuron culture Neuroscience Medium 25010400

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence. Biochemical and biophysical research communications 217 2610682
2018 Neural Stem Cells Behave as a Functional Niche for the Maturation of Newborn Neurons through the Secretion of PTN. Neuron 87 30497772
2005 Increased keratinocyte proliferation by JUN-dependent expression of PTN and SDF-1 in fibroblasts. Journal of cell science 84 15840658
2014 Functional receptors and intracellular signal pathways of midkine (MK) and pleiotrophin (PTN). Biological & pharmaceutical bulletin 76 24694599
1990 Heparin-binding neurotrophic factor (HBNF) and MK, members of a new family of homologous, developmentally regulated proteins. Biochemical and biophysical research communications 67 1700712
2019 Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis. Life sciences 61 31521692
2019 Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTPβ/ζ Axis: Relevance in Therapeutic Development. Frontiers in pharmacology 59 31031625
1992 Expression of the HBNF (heparin-binding neurite-promoting factor) gene in the brain of fetal, neonatal and adult rat: an in situ hybridization study. Brain research. Developmental brain research 55 1477961
1991 HBNF and MK, members of a novel gene family of heparin-binding proteins with potential roles in embryogenesis and brain function. Progress in growth factor research 53 1773041
2010 Lung cancer cell migration is regulated via repressing growth factor PTN/RPTP β/ζ signaling by menin. Oncogene 51 20639902
2000 Influence of the human endogenous retrovirus-like element HERV-E.PTN on the expression of growth factor pleiotrophin: a critical role of a retroviral Sp1-binding site. Oncogene 42 10962555
2018 Chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis promote chemoresistance by activating the NF-κB pathway in breast cancer cells. Cell communication and signaling : CCS 39 30497491
2005 Effects of pleiotrophin (PTN) over-expression on mouse long bone development, fracture healing and bone repair. Calcified tissue international 38 15812580
2020 Long noncoding RNA OIP5-AS1 mediates resistance to doxorubicin by regulating miR-137-3p/PTN axis in osteosarcoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 37 32460190
2019 The PTN-PTPRZ signal activates the AFAP1L2-dependent PI3K-AKT pathway for oligodendrocyte differentiation: Targeted inactivation of PTPRZ activity in mice. Glia 37 30667096
2020 Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer. British journal of cancer 33 33288843
2002 Pleiotrophin (PTN) and midkine (MK) mRNA expression in eutopic and ectopic endometrium in advanced stage endometriosis. Molecular human reproduction 33 11912283
2005 Miple1 and miple2 encode a family of MK/PTN homologues in Drosophila melanogaster. Development genes and evolution 31 16220264
1991 Isolation from bovine brain and structural characterization of HBNF, a heparin-binding neurotrophic factor. Growth factors (Chur, Switzerland) 31 2049182
2020 Down-regulation of circ-PTN suppresses cell proliferation, invasion and glycolysis in glioma by regulating miR-432-5p/RAB10 axis. Neuroscience letters 30 32629066
2019 miR-627-3p inhibits osteosarcoma cell proliferation and metastasis by targeting PTN. Aging 30 31413208
2022 Luteolin attenuates the chemoresistance of osteosarcoma through inhibiting the PTN/β-catenin/MDR1 signaling axis by upregulating miR-384. Journal of bone oncology 27 35493691
2019 Genome-wide screening identifies oncofetal lncRNA Ptn-dt promoting the proliferation of hepatocellular carcinoma cells by regulating the Ptn receptor. Oncogene 23 30643194
2003 The angiogenic peptide pleiotrophin (PTN/HB-GAM) is expressed in fracture healing: an immunohistochemical study in rats. Archives of orthopaedic and trauma surgery 23 14586627
2021 circ_PTN contributes to -cisplatin resistance in glioblastoma via PI3K/AKT signaling through the miR-542-3p/PIK3R3 pathway. Molecular therapy. Nucleic acids 22 34853725
2015 Size-dependent electronic structure controls activity for ethanol electro-oxidation at Ptn/indium tin oxide (n = 1 to 14). Physical chemistry chemical physics : PCCP 22 26018430
2014 PTN signaling: Components and mechanistic insights in human ovarian cancer. Molecular carcinogenesis 22 25418856
1999 Glycosaminoglycans promote HARP/PTN dimerization. Biochemical and biophysical research communications 21 10600521
2020 CircRNA-PTN Sponges miR-326 to Promote Proliferation in Hepatocellular Carcinoma. OncoTargets and therapy 20 32581550
2009 Pleiotrophin (PTN) is expressed in vascularized human atherosclerotic plaques: IFN-{gamma}/JAK/STAT1 signaling is critical for the expression of PTN in macrophages. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20 19917672
2013 Anaplastic lymphoma kinase: "Ligand Independent Activation" mediated by the PTN/RPTPβ/ζ signaling pathway. Biochimica et biophysica acta 19 23777859
2012 Pleiotrophin (PTN) expression and function and in the mouse mammary gland and mammary epithelial cells. PloS one 18 23077670
2018 Reactions of Cyclometalated Platinum(II) [Pt(N∧C)(PR3)Cl] Complexes with Imidazole and Imidazole-Containing Biomolecules: Fine-Tuning of Reactivity and Photophysical Properties via Ligand Design. Inorganic chemistry 17 30376305
2017 Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone. Journal of cellular physiology 17 28657144
2017 miR-182 aids in receptive endometrium development in dairy goats by down-regulating PTN expression. PloS one 16 28678802
1993 Genomic organization of the human HBNF gene and characterization of an HBNF variant protein as a splice mutant. Biochemical and biophysical research communications 16 8484754
2023 Single-cell RNA sequencing reveals the mediatory role of cancer-associated fibroblast PTN in hepatitis B virus cirrhosis-HCC progression. Gut pathogens 15 37259127
2021 RNA binding protein GNL3 up-regulates IL24 and PTN to promote the development of osteoarthritis. Life sciences 15 33358901
2021 The ERK/CREB/PTN/syndecan-3 pathway involves in heparin-mediated neuro-protection and neuro-regeneration against cerebral ischemia-reperfusion injury following cardiac arrest. International immunopharmacology 15 34153666
2012 Synthesis, characterization, and DNA-binding studies of ruthenium complexes [Ru(tpy)(ptn)]2+ and Ru(dmtpy)(ptn)]2+. Journal of inorganic biochemistry 15 22687492
2013 Intranasal immunization with W 80 5EC adjuvanted recombinant RSV rF-ptn enhances clearance of respiratory syncytial virus in a mouse model. Human vaccines & immunotherapeutics 14 24326268
2014 Cocaine- and amphetamine-regulated transcript facilitates the neurite outgrowth in cortical neurons after oxygen and glucose deprivation through PTN-dependent pathway. Neuroscience 12 25010400
2022 LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma. Journal of clinical laboratory analysis 10 35588441
2024 Astrocyte-derived PTN alleviates deficits in hippocampal neurogenesis and cognition in models of multiple sclerosis. Stem cell reports 9 39729991
2020 PTN-PTPRZ signalling is involved in deer antler stem cell regulation during tissue regeneration. Journal of cellular physiology 9 33111346
2020 Up-regulation of miR-137 can inhibit PTN in target manner to regulate PTN/PTPRZ pathway to prevent cognitive dysfunction caused by propofol. American journal of translational research 9 33312384
2011 PAd-shRNA-PTN reduces pleiotrophin of pancreatic cancer cells and inhibits neurite outgrowth of DRG. World journal of gastroenterology 9 21677838
2023 The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment. Journal of proteome research 8 37611228
2002 Pd(II)- and Pt(II)-cimetidine complexes. Crystal structure of trans-[Pt(N,S-cimetidine)(2)]Cl(2)(*)12H(2)O. Journal of inorganic biochemistry 8 12062128
2023 Implication of the PTN/RPTPβ/ζ Signaling Pathway in Acute Ethanol Neuroinflammation in Both Sexes: A Comparative Study with LPS. Biomedicines 7 37238989
2018 Hmgb3 Induces the Differentiation of Uterine Stromal Cells Through Targeting Ptn. Reproductive sciences (Thousand Oaks, Calif.) 7 30081728
1995 Chromosomal assignment of the heparin-binding cytokine genes MDK and PTN in mouse and man. Cytogenetics and cell genetics 7 7835084
1992 Anti-viral activity of human recombinant heparin-binding proteins HBNF and MK. Biochemical and biophysical research communications 7 1335242
2025 PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior. Nature communications 6 40069581
2024 PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1. Biological research 6 39285301
2020 Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells. Cancer management and research 6 32801858
2025 PTN secreted by cardiac fibroblasts promotes myocardial fibrosis and inflammation of pressure overload-induced hypertrophic cardiomyopathy through the PTN-SDC4 pathway. Life sciences 5 39765325
2024 A novel risk classification model integrating CEA, ctDNA, and pTN stage for stage 3 colon cancer: a post hoc analysis of the IDEA-France trial. The oncologist 4 39011625
2025 Tenacissoside G reverses paclitaxel resistance by inhibiting Src/PTN/P-gp signaling axis activation in ovarian cancer cells. Journal of natural medicines 3 40195205
2024 Mea6/cTAGE5 cooperates with TRAPPC12 to regulate PTN secretion and white matter development. iScience 3 38439956
2024 Pt-N catalytic centres concisely enhance interfacial charge transfer in amines functionalized Pt@MOFs for selective conversion of CO2 to CH4. Journal of colloid and interface science 2 38850864
2024 Effects of pleiotrophin (PTN) on the FAK inhibitor Y15 in breast cancer cells. International journal of biological macromolecules 2 39322128
2024 scRNA-Seq Analysis Revealed CAFs Regulating HCC Cells via PTN Signaling. Journal of hepatocellular carcinoma 2 39582814
2019 Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer. In vivo (Athens, Greece) 2 31662522
2007 [Construction of the recombinant adenovirus mediated shRNA to silence PTN in pancreatic carcinoma and the effect of DRGn on neurite in vitro]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 2 17825221
1992 [Clinical pathology of hypopharyngeal cancer--comparison between TN and pTN]. Nihon Jibiinkoka Gakkai kaiho 2 1569513
2026 Added value of tumor-stroma ratio to postsurgery circulating tumor DNA and pTN stage in risk stratification of patients with stage III colon cancer treated with adjuvant chemotherapy. ESMO open 1 41483629
2026 Cardiac PTN-SIRT1 axis alleviates oxidative stress and promotes mitochondrial energy reprogramming to mitigate doxorubicin-induced cardiotoxicity through AMPK/PGC1α signaling. Acta biochimica et biophysica Sinica 1 41640280
2025 The lncrna HMMR-AS1 promotes the malignant progression of ovarian cancer cells by regulating the miR-627-3p/PTN axis. Journal of ovarian research 1 40462168
2025 Targeting the HNRNPA2B1/HDGF/PTN Axis to Overcome Radioresistance in Non-Small Cell Lung Cancer. Antioxidants & redox signaling 1 40643435
2023 Pt-N Coordination Rendering the Chemotherapeutic Agent with Photoactivated ROS Generation and Self-Reporting Cell Uptake. ACS applied bio materials 1 36949576
2020 Positive association between PTN polymorphisms and schizophrenia in Northeast Chinese Han population. Psychiatric genetics 1 32868733
2016 Investigating the mechanism of the selective hydrogenation reaction of cinnamaldehyde catalyzed by Ptn clusters. Journal of molecular modeling 1 27444877
2026 Deciphering Key Descriptors for Scaling Relationships in Graphene-Supported Ptn Clusters via Machine Learning. Small (Weinheim an der Bergstrasse, Germany) 0 41615214
2026 ICAM2 loss drives 5-fluorouracil resistance via TGF-β/Smad/SP1/PTN-dependent apoptosis evasion and macrophage remodeling in gastric cancer. World journal of gastroenterology 0 41693979
2026 PTN/IGF-2 signaling modulates endometrial decidualization and immune cell trafficking to facilitate pregnancy maintenance. Frontiers in immunology 0 41948339
2025 Targeting the PTN/PTPRZ1-ROS Pathway to Promote Bone Regeneration. Biomedicines 0 40149671
2020 Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells [Retraction]. Cancer management and research 0 33116829

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