Affinage

EDN3

Endothelin-3 · UniProt P14138

Length
238 aa
Mass
25.5 kDa
Annotated
2026-06-09
54 papers in source corpus 17 papers cited in narrative 17 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EDN3 (endothelin-3) is a secreted peptide ligand that signals predominantly through the ETB receptor (EDNRB) — and the EDNRB2 paralog in non-mammalian species — to govern the development of neural crest-derived lineages, including enteric neurons and melanocytes (PMID:7509343, PMID:31351053, PMID:21538684). During enteric nervous system development, EDN3 maintains the precursor pool by inhibiting premature GDNF-driven neuronal differentiation (PMID:9578621), and it acts in a coordinate, dose-balanced interaction with Sox10 required for gut colonization by enteric crest cells and for melanocyte development, with loss of signaling causing apoptosis and impaired migration of vagal neural crest cells (PMID:16650841). In the melanocyte lineage, EDN3/EDNRB signaling activates melanocyte stem cells to regenerate follicular and epidermal melanocytes (PMID:28779103) and drives melanoblast migration and invasion (PMID:21538684). At the receptor level, the third transmembrane domain residue Lys-181 of ETB is critical for high-affinity EDN3 binding but dispensable for G-protein coupling (PMID:1282984), and EDN3 engages downstream effectors including intracellular Ca2+/calmodulin-dependent nitric oxide/cGMP production (PMID:7509343) and Gi/Gq-dependent MAPK/ERK activation that upregulates c-fos and c-jun (PMID:18362896). EDN3 also functions in non-developmental contexts as a co-mitogen for vascular smooth muscle cells (PMID:2102088) and a modulator of glomerular, astroglial, and granulosa cell physiology (PMID:7509343, PMID:10516091, PMID:9659283). The gene is silenced by promoter hypermethylation in breast and cervical carcinomas, where re-expression suppresses proliferation, migration, and invasion, consistent with a tumor-suppressor role (PMID:19527488, PMID:36824133), while EDN3 overexpression in the melanoma microenvironment promotes immune evasion via Treg expansion through EDNRB (PMID:34288510).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1991 Medium

    Established that EDN3 is recognized by distinct endothelin receptor subtypes, distinguishing a high-affinity ET-1/ET-2-preferring site from a lower-affinity site binding all three isoforms equally — the pharmacological foundation for receptor-selective EDN3 signaling.

    Evidence Radioligand binding and dissociation kinetics in cultured rat aortic smooth muscle cells

    PMID:1725299

    Open questions at the time
    • Did not molecularly identify the receptor genes corresponding to each binding subtype
    • Binding kinetics alone do not define downstream signaling consequences
  2. 1992 High

    Mapped a specific ETB receptor residue controlling EDN3 affinity, showing that ligand binding and G-protein coupling are separable functions of the receptor.

    Evidence Site-directed mutagenesis (Lys181Asp) of rat ETB expressed in COS-7 cells with binding and inositol phosphate assays

    PMID:1282984

    Open questions at the time
    • Single residue tested in one receptor subtype
    • Does not address EDN3-specific (vs ET-1) determinants of selectivity
  3. 1994 High

    Defined a downstream signaling axis for EDN3, linking ETB activation to intracellular Ca2+/calmodulin-dependent nitric oxide and cGMP production independent of L-type Ca2+ channels.

    Evidence cGMP accumulation assays with selective agonist/antagonist and inhibitor panel in rat glomeruli and mesangial cells

    PMID:7509343

    Open questions at the time
    • Tissue-restricted to renal cells
    • Does not connect this pathway to developmental phenotypes
  4. 1998 Medium

    Revealed EDN3's core developmental function: maintaining the enteric neural precursor pool by antagonizing GDNF-stimulated neuronal differentiation, with context-dependent effects on proliferation.

    Evidence In vitro culture of immunoaffinity-isolated quail enteric neural crest precursors with proliferation and neurite assays

    PMID:9578621

    Open questions at the time
    • In vitro avian system; not validated in vivo here
    • Molecular mechanism of differentiation inhibition not defined
  5. 1999 Medium

    Demonstrated EDN3 acts through ETB-restricted signaling to inhibit astroglial gap junction communication, contrasting with ET-1's dual-receptor action.

    Evidence Dye diffusion, Ca2+ imaging and receptor-subtype pharmacology in cultured rat astrocytes

    PMID:10516091

    Open questions at the time
    • Single cell-type model
    • Physiological significance in the nervous system not established
  6. 1999 Medium

    Explained at the structural level why big ET-3 is a poor ECE-1 substrate, attributing reduced processing efficiency to local sequence differences near the cleavage site rather than global fold differences.

    Evidence CD spectroscopy, thermal denaturation and homology modeling of big ET-3 vs big ET-1

    PMID:10026250

    Open questions at the time
    • No direct cleavage assay or mutagenesis to test the proposed determinants
    • Modeling-based structural inference only
  7. 2006 High

    Placed EDN3 in a balanced genetic network with Sox10 required for enteric nervous system and melanocyte development, showing loss of signaling causes neural crest apoptosis and impaired gut colonization.

    Evidence Sox10;Edn3 and Sox10;Ednrb double-mutant mouse phenotyping with apoptosis, proliferation, and differentiation markers

    PMID:16650841

    Open questions at the time
    • Genetic interaction does not specify the molecular crosstalk between EDN3 and Sox10
    • Does not resolve cell-autonomous vs non-autonomous contributions
  8. 2008 Medium

    Resolved the EDN3-to-ERK signaling cascade, showing convergence of Gi/Src and Gq/PKC inputs on Ras/Raf to drive immediate-early gene expression and cell growth.

    Evidence Pharmacological pathway dissection with MAPK phospho-blots in JAR and Jeg-3 choriocarcinoma cells

    PMID:18362896

    Open questions at the time
    • Cancer cell line model
    • Relevance to normal neural crest growth not tested
  9. 2009 Medium

    Identified promoter hypermethylation as the predominant mechanism silencing EDN3 in breast cancer, implicating EDN3 loss in tumorigenesis.

    Evidence Methylation-specific PCR, expression analysis, and demethylating-agent rescue in breast cancer cohorts and cell lines

    PMID:19527488

    Open questions at the time
    • Correlative epigenetic silencing; tumor-suppressor function not directly tested here
    • Mechanism by which EDN3 loss promotes cancer not addressed
  10. 2011 Medium

    Showed EDN3/EDNRB2 signaling directs melanoblast migration in vivo and enhances invasive capacity, extending the developmental role to melanocyte positioning.

    Evidence In situ hybridization, morpholino knockdown and dominant-negative perturbation plus in vitro invasion assay in Xenopus

    PMID:21538684

    Open questions at the time
    • EDNRB2 is a non-mammalian paralog; mammalian generalization uncertain
    • Downstream migratory effectors not identified
  11. 2017 High

    Demonstrated that endogenous EDN3 activates melanocyte stem cells via EDNRB to regenerate melanocytes, establishing a physiological adult role in pigmentation.

    Evidence Mouse epilation model with genetic and pharmacological EDNRB blockade and melanocyte marker immunofluorescence

    PMID:28779103

    Open questions at the time
    • Stem cell activation mechanism downstream of EDNRB not detailed
    • Source cells of EDN3 mapped but signaling kinetics not resolved
  12. 2019 Medium

    Clarified EDN3 receptor selectivity across endothelin receptors, showing it activates both EDNRB and EDNRB2 (but not EDNRA) to engage calcium, ERK, and cAMP/PKA pathways.

    Evidence Heterologous expression of chicken EDNRs in HEK293 cells with luciferase pathway reporters

    PMID:31351053

    Open questions at the time
    • Avian receptors; mammalian receptor coupling may differ
    • Does not link individual pathways to specific biological outputs
  13. 2021 Medium

    Uncovered a tumor-microenvironment role in which EDN3 overexpression promotes melanoma immune evasion by expanding regulatory T cells through EDNRB.

    Evidence K5-Edn3 transgenic melanoma model, flow cytometry, in vitro Treg proliferation assay and BQ-788 EDNRB blockade

    PMID:34288510

    Open questions at the time
    • Treg expansion mechanism downstream of EDNRB not defined
    • Direct vs indirect effects on dendritic cells not separated
  14. 2023 Medium

    Extended the epigenetic-silencing/tumor-suppressor model to cervical cancer, showing EDN3 re-expression suppresses proliferation, migration, and invasion.

    Evidence Pyrosequencing, 5-Azacytidine treatment, and gain-of-function functional assays in cervical cancer cell lines

    PMID:36824133

    Open questions at the time
    • Mechanism of growth suppression by EDN3 not defined
    • In vitro cell lines only; no in vivo tumor model
  15. 2025 Medium

    Connected EDN3/EDNRB signaling to a cellular mechanism for migration, showing it gates intracellular calcium activity that controls enteric neural crest cell contractility and traction force.

    Evidence Live calcium imaging in mouse gut explants with channel/IP3R inhibitors and traction force microscopy (preprint)

    PMID:bio_10.1101_2025.10.23.684245

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Links between EDNRB and the specific ion channels not molecularly established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EDN3/EDNRB signaling outputs (Ca2+, ERK, cAMP, NO/cGMP) are selectively coupled to distinct biological outcomes — precursor maintenance versus migration versus immune modulation — and the molecular basis of EDN3's tumor-suppressor activity remain unresolved.
  • No unified model linking pathway choice to cellular outcome
  • Tumor-suppressor mechanism of EDN3 undefined
  • Direct molecular crosstalk with Sox10 not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3
Partners
EDNRBEDNRB2

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ET-3 inhibits neuronal differentiation of enteric neural precursor cells in vitro, overriding GDNF-stimulated differentiation into neurons, thereby maintaining the precursor cell pool. At low cell density or in defined medium, ET-3 reduced cell proliferation; at high density with serum, ET-3 and GDNF had an additive proliferative effect. In vitro culture of HNK-1-immunoaffinity-isolated enteric neural crest precursors from quail embryos; cell counting, neurite quantification, proliferation assays Developmental biology Medium 9578621
1990 ET-3 (along with ET-1 and ET-2) functions as a co-mitogen for rat vascular smooth muscle cells, potentiating DNA synthesis induced by PDGF but unable to initiate DNA synthesis alone. ET-3 was less potent than ET-1 and ET-2 in this co-mitogenic effect. BrdU incorporation assay in cultured rat vascular smooth muscle cells; image analysis of stained nuclei Atherosclerosis Medium 2102088
2006 Genetic epistasis experiments in Sox10;Edn3 double mutant mice demonstrate that Edn3 and Sox10 act in a coordinate and balanced interaction required for normal enteric nervous system (ENS) and melanocyte development. Partial loss of Ednrb in Sox10 heterozygous mice impairs gut colonization by enteric crest cells at all stages, and increased apoptosis was found in vagal neural crest cells outside the gut in double mutants. Double mutant mouse phenotype analysis (Sox10;Edn3 and Sox10;Ednrb); immunohistochemistry for apoptosis, cell proliferation, neuronal/glial differentiation markers in neural crest cells Developmental biology High 16650841
1994 ET-3 stimulates cGMP production in rat glomeruli and cultured mesangial cells via ETB receptor activation, with the mechanism dependent on intracellular Ca2+/calmodulin-mediated nitric oxide (NO) production; L-type Ca2+ channel influx was not required. cGMP accumulation assays in isolated rat glomerulus and cultured mesangial cells; pharmacological dissection using ETB agonist (IRL 1620), ETA antagonist (BQ123), NOS inhibitor (L-NMMA), BAPTA/AM, W-7, nicardipine The Journal of clinical investigation High 7509343
1999 ET-3 inhibits astroglial gap junction permeability and intercellular Ca2+ signaling exclusively via ETB receptors (effects blocked by ETB antagonist, not ETA antagonist), whereas ET-1 inhibits these same processes via both ETA and ETB receptors. ET-3 and ET-1 also induce intracellular Ca2+ increases in astrocytes with distinct response patterns depending on receptor subtype. Dye diffusion assays for gap junction permeability, intracellular Ca2+ imaging, pharmacological receptor subtype dissection with selective antagonists; cultured rat hippocampal and striatal astrocytes The American journal of physiology Medium 10516091
2017 Epilation triggers upregulation of endogenous EDN3 in dermal papilla, secondary hair germ cells, and epidermis, which activates melanocyte stem cells (McSCs) via EDNRB signaling to regenerate follicular and epidermal melanocytes, causing skin and hair hyperpigmentation. Genetic and pharmacological blockade of EDNRB significantly inhibited McSC activation and hyperpigmentation after epilation. Mouse epilation model; transgenic and pharmacological (EDNRB inhibitor) disruption of EDNRB in vivo; immunofluorescence for melanocyte markers Scientific reports High 28779103
2008 ET-3 (and ET-1), acting via ETB receptors on human choriocarcinoma cells, activates p42/44 MAPK (ERK1/2) through Gi- and Gq-dependent pathways involving Src (downstream of Gi) and PKC (downstream of Gq) converging at Ras/Raf. This leads to transcriptional upregulation of c-fos and c-jun and increased cell growth. Western blot for MAPK phosphorylation; pharmacological inhibition of Gi, Gq, Src, PKC, Ras/Raf in JAR and Jeg-3 choriocarcinoma cell lines; receptor expression confirmed by RT-PCR British journal of pharmacology Medium 18362896
2009 EDN3 promoter hypermethylation (detected in 70% of primary breast carcinomas) is the predominant mechanism silencing EDN3 gene expression in breast cancer; treatment with 5-aza-2'-deoxycytidine and trichostatin A restored EDN3 mRNA expression in breast cancer cell lines in vitro. Methylation-specific PCR, Northern blot, real-time PCR, tissue microarray; demethylating agent treatment (5-aza-2'-deoxycytidine + trichostatin A) in breast cancer cell lines Breast cancer research : BCR Medium 19527488
2011 ET3/Ednrb2 signaling is required for melanoblast migration in Xenopus laevis: Ednrb2 is expressed by melanoblasts from pre-migratory stages, ET3 is expressed near melanoblast destinations, and aberrant ET3/Ednrb2 signaling disrupts melanoblast migration in vivo while ET3 enhances melanoblast invasive ability in vitro. In situ hybridization for Ednrb2 and ET3 expression; in vivo morpholino-mediated knockdown and dominant-negative approaches; in vitro invasion assay with ET3 Developmental dynamics Medium 21538684
1991 ET-3 binds to two distinct receptor subtypes on rat aortic smooth muscle cells: a high-affinity ET-1/ET-2-preferring receptor (80–85% of sites, irreversible binding, subject to downregulation) and a lower-affinity subtype (15–20%) that binds all three ET isoforms with equal affinity in a reversible manner and is insensitive to downregulation. Radioligand binding assay ([125I]ET-1, [125I]ET-2, [125I]ET-3) with competition and dissociation kinetics; downregulation by pre-exposure to ET isoforms in cultured rat aortic smooth muscle cells Journal of cardiovascular pharmacology Medium 1725299
1992 Substitution of lysine-181 to aspartic acid in the third transmembrane domain of the rat ETB receptor selectively reduces high-affinity binding of ET-3 (IC50 increases ~200-fold), while still permitting full inositol phosphate signaling at saturating ET-3 concentrations, indicating this residue is critical for ligand affinity but not G-protein coupling. Site-directed mutagenesis of ETB receptor; transient expression in COS-7 cells; radioligand displacement binding assay ([125I]ET-1); inositol phosphate accumulation assay Journal of cardiovascular pharmacology High 1282984
1999 Big ET-3 and big ET-1 adopt similar secondary structures and overall folds (assessed by CD spectroscopy and homology modeling), but differ in the C-terminal region (residues 34–41 in big ET-3 vs. 34–38 in big ET-1) near the cleavage site. The sequence differences in the local region around the ECE-1 cleavage site (QTVP in big ET-3 vs. HVVP in big ET-1) account for the substantially lower efficiency of ECE-1 processing of big ET-3 relative to big ET-1. Circular dichroism spectroscopy; thermal denaturation; homology modeling and structural superposition Biochemistry Medium 10026250
2021 Edn3 overexpression in the skin microenvironment promotes immune evasion by melanoma tumors via EDNRB signaling: tumors in K5-Edn3 transgenic mice (keratinocyte-driven Edn3 overexpression) were larger, with higher numbers of regulatory T cells (Tregs) and dendritic cells. Edn3 directly increased Treg proliferation and FOXP3 expression in vitro. Pharmacological EDNRB blockade (BQ-788) reduced tumor growth. Transgenic K5-Edn3 mouse model; subcutaneous melanoma injection; flow cytometry for immune cell populations; in vitro Treg proliferation assay; EDNRB antagonist (BQ-788) treatment Pigment cell & melanoma research Medium 34288510
1998 ET-3, acting via ETB receptor, inhibits estrogen and cAMP production by rat granulosa cells; this inhibitory effect is not mediated by the ETA receptor (BQ-123 had no effect), is not mediated by prostanoids (indomethacin had no effect), and ETB-selective agonist sarafotoxin-S6c mimicked the effect. ET-3 was more potent than ET-1 in suppressing estrogen production. Hormone (estrogen, cAMP) production assays in isolated rat granulosa cells; pharmacological dissection with ETA antagonist (BQ-123), ETB agonist (sarafotoxin-S6c), and indomethacin The Journal of endocrinology Medium 9659283
2025 Migrating enteric neural crest cells (ENCCs) in mice exhibit endogenous EDN3/EDNRB-gated intracellular calcium activity, mediated by chloride channels, T-type Ca2+ channels (CaV3.2/CACNA1H), and IP3-sensitive intracellular Ca2+ store release. Inhibiting Ca2+ activity caused ENCC migration defects, while stimulating Ca2+ activity promoted migration by increasing ENCC contractility and traction force to the extracellular matrix. Live calcium imaging of ENCCs in mouse gut explants; pharmacological inhibition of chloride channels, T-type Ca2+ channels, and IP3 receptors; traction force microscopy; ENCC migration assays bioRxivpreprint Medium bio_10.1101_2025.10.23.684245
2023 EDN3 promoter methylation silences EDN3 expression in cervical cancer; treatment with 5-Azacytidine (DNMT1 inhibitor) restored EDN3 expression. Overexpression of EDN3 in cervical cancer cell lines inhibited proliferation, clone formation, migration, and invasion. Pyrosequencing of EDN3 promoter CpG sites; 5-Azacytidine treatment in cell lines; EdU assay, wound-healing assay, clone formation, transwell invasion assay after EDN3 overexpression Frontiers in oncology Medium 36824133
2019 Chicken EDN3 peptide activates both EDNRB and EDNRB2 receptors with similar potencies, stimulating intracellular calcium, MAPK/ERK, and cAMP/PKA signaling pathways, whereas EDNRA is preferentially activated by EDN1 and EDN2 but not EDN3. Heterologous expression of chicken EDNRs in HEK293 cells; luciferase reporter assays for calcium, MAPK/ERK, and cAMP/PKA pathway activation General and comparative endocrinology Medium 31351053

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 GDNF and ET-3 differentially modulate the numbers of avian enteric neural crest cells and enteric neurons in vitro. Developmental biology 190 9578621
1990 The endothelin peptides ET-1, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor for vascular smooth muscle cells. Atherosclerosis 126 2102088
2006 Interactions between Sox10, Edn3 and Ednrb during enteric nervous system and melanocyte development. Developmental biology 105 16650841
1991 Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3. American journal of human genetics 94 2018043
2001 EDNRB/EDN3 and Hirschsprung disease type II. Pigment cell research 80 11434563
1994 Endothelin (ET)-3 stimulates cyclic guanosine 3',5'-monophosphate production via ETB receptor by producing nitric oxide in isolated rat glomerulus, and in cultured rat mesangial cells. The Journal of clinical investigation 77 7509343
1999 Distinct pharmacological properties of ET-1 and ET-3 on astroglial gap junctions and Ca(2+) signaling. The American journal of physiology 56 10516091
2001 Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease. Gut 55 11302967
1991 Effects of endothelins (ET-1, ET-2 and ET-3) in the rabbit eye; role of prostaglandins. European journal of pharmacology 54 2060603
2010 New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. Genetics in medicine : official journal of the American College of Medical Genetics 44 20009762
2009 Frequent loss of endothelin-3 (EDN3) expression due to epigenetic inactivation in human breast cancer. Breast cancer research : BCR 44 19527488
2008 Pathogenomic analysis of the common bovine Staphylococcus aureus clone (ET3): emergence of a virulent subtype with potential risk to public health. The Journal of infectious diseases 42 18177250
2001 Evidence that ET-1, but not ET-3 and S6b, ET(A)-receptor mediated contractions in isolated rat mesenteric arteries are modulated by co-activation of ET(B) receptors. British journal of pharmacology 35 11454667
2003 Spectroscopic study of [Fe2O2(5-Et3-TPA)2]3+: nature of the Fe2O2 diamond core and its possible relevance to high-valent binuclear non-heme enzyme intermediates. Journal of the American Chemical Society 34 12797809
2017 Epilation induces hair and skin pigmentation through an EDN3/EDNRB-dependent regenerative response of melanocyte stem cells. Scientific reports 33 28779103
2008 Endothelin (ET)-1 and ET-3 promote expression of c-fos and c-jun in human choriocarcinoma via ET(B) receptor-mediated G(i)- and G(q)-pathways and MAP kinase activation. British journal of pharmacology 33 18362896
2001 Potentiation of insulin-related signal transduction by a novel protein-tyrosine phosphatase inhibitor, Et-3,4-dephostatin, on cultured 3T3-L1 adipocytes. The Journal of biological chemistry 33 11342532
1991 Binding sites for 125I ET-1, ET-2, ET-3 and vasoactive intestinal contractor are present in adult rat brain and neurone-enriched primary cultures of embryonic brain cells. Brain research 33 1657290
2006 Aerobic culture of Propionibacterium freudenreichii ET-3 can increase production ratio of 1,4-dihydroxy-2-naphthoic acid to menaquinone. Journal of bioscience and bioengineering 30 16935247
2019 Genomic Analysis Reveals Pleiotropic Alleles at EDN3 and BMP7 Involved in Chicken Comb Color and Egg Production. Frontiers in genetics 27 31316551
2011 ET3/Ednrb2 signaling is critically involved in regulating melanophore migration in Xenopus. Developmental dynamics : an official publication of the American Association of Anatomists 26 21538684
1991 Localization of endothelin-1 (ET-1), ET-2, and ET-3, mouse VIC, and sarafotoxin S6b binding sites in mammalian heart and kidney. Journal of cardiovascular pharmacology 25 1725315
2001 Differential effects of ET-1, ET-2, and ET-3 on pancreatic microcirculation, tissue integrity, and inflammation. Digestive diseases and sciences 24 11414314
1999 A heterozygous frameshift mutation in the endothelin-3 (EDN-3) gene in isolated Hirschsprung's disease. Pediatric research 22 10231870
1995 Temporal expression of ECE-1, ET-1, ET-3, ETA, and ETB receptor mRNAs after balloon angioplasty in the rat. Journal of cardiovascular pharmacology 22 8587369
1991 Binding characteristics of endothelin isoforms (ET-1, ET-2, and ET-3) in vascular smooth muscle cells. Journal of cardiovascular pharmacology 22 1725299
2019 Endothelins (EDN1, EDN2, EDN3) and their receptors (EDNRA, EDNRB, EDNRB2) in chickens: Functional analysis and tissue distribution. General and comparative endocrinology 21 31351053
2008 Electrochemical regulation of the end-product profile in Propionibacterium freudenreichii ET-3 with an endogenous mediator. Biotechnology and bioengineering 19 18454500
2009 Contribution of RET, NTRK3 and EDN3 to the expression of Hirschsprung disease in a multiplex family. Journal of medical genetics 17 19556619
2013 [Hereditary hypomelanocytoses: the role of PAX3, SOX10, MITF, SNAI2, KIT, EDN3 and EDNRB genes]. Postepy higieny i medycyny doswiadczalnej (Online) 16 24379252
2018 A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses. Physiological reports 13 29845762
1995 Thirteen genes (Cebpb, E2f1, Tcf4, Cyp24, Pck1, Acra4, Edn3, Kcnb1, Mc3r, Ntsr, Cd40, Plcg1 and Rcad) that probably lie in the distal imprinting region of mouse chromosome 2 are not monoallelically expressed. Genetical research 13 7781998
2003 Clinical relationship between EDN-3 gene, EDNRB gene and Hirschsprung's disease. World journal of gastroenterology 11 14669347
1995 ET-3 is extracted by and induces potent vasoconstriction in human splanchnic and renal vasculatures. Journal of applied physiology (Bethesda, Md. : 1985) 11 8567570
1991 The gene for the novel vasoactive peptide endothelin 3 (EDN3) is localized to human chromosome 20q13.2-qter. Genomics 11 1889823
1998 Endothelin (ET)-1 and ET-3 inhibit estrogen and cAMP production by rat granulosa cells in vitro. The Journal of endocrinology 10 9659283
1996 Et-1 and Et-3 actions mediated by cloned ETA endothelin receptors exhibit different sensitivities to BQ-123. Biochemical and biophysical research communications 10 8694806
1992 ET-3 sensitive reduction of tissue blood flow in rat liver. Life sciences 10 1325015
1991 Bronchopulmonary and pressor activities of endothelin-1 (ET-1), ET-2, ET-3, and big ET-1 in the guinea pig. Journal of cardiovascular pharmacology 10 1725370
1994 Phosphoinositide turnover signaling stimulated by ET-3 in endothelial cells from spontaneously hypertensive rats. The American journal of physiology 9 8092306
2010 Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects. Regulatory toxicology and pharmacology : RTP 8 21172397
2001 Effect of vasoactive peptides on Tetrahymena. chemotactic properties of endothelins (ET-1, ET-2, ET-3, fragment 11-21 of ET-1 and big endothelin-1): a short-term inducible signalling mechanism of chemotaxis. Cell biology international 8 11913962
1992 Substitution of lysine-181 to aspartic acid in the third transmembrane region of the endothelin (ET) type B receptor selectively reduces its high-affinity binding with ET-3 peptide. Journal of cardiovascular pharmacology 8 1282984
2021 The immunosuppressive role of Edn3 overexpression in the melanoma microenvironment. Pigment cell & melanoma research 6 34288510
2025 Transcriptomic Profiling Unveils EDN3+ Meningeal Fibroblasts as Key Players in Sturge-Weber Syndrome Pathogenesis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39921427
2010 Analysis of RET, ZEB2, EDN3 and GDNF genomic rearrangements in central congenital hyperventilation syndrome patients by multiplex ligation-dependent probe amplification. Annals of human genetics 5 20456320
2023 Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity. Nature communications 4 37452013
2011 Safety evaluation of Propionibacterium freudenreichii ET-3 culture. Regulatory toxicology and pharmacology : RTP 3 21406207
2023 Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion. Frontiers in oncology 2 36824133
1999 Do the structures of big ET-1 and big ET-3 adopt a similar overall fold? Consequences for endothelin converting enzyme specificity. Biochemistry 2 10026250
2025 Stemness-associated WNT3A and EDN3 as key regulators of tumor progression and immunotherapy efficacy in LUAD. International journal of surgery (London, England) 1 40696931
2026 A cis-regulatory mutation in the EDN3 promoter drives coordinated formation of comb and skin color in Anyi gray chickens. Poultry science 0 41850061
2026 Differential Expression of MITF, WNT3A, SLC7A11, and EDN3 in the Shoulder 'Bider Marking' of Dun Mongolian Horses. Animals : an open access journal from MDPI 0 41897944
2003 [Expression of ET-3 in hippocampal CA1 of ovariectomied mice after cerebral ischemia/reperfusion]. Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 0 14653120

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