Edn1

Summary

Gene Symbol: Edn1
Description: endothelin 1
Alias: ET-1, PPET1, preproET, endothelin-1, preproendothelin-1
Species: mouse
Products:     Edn1

Top Publications

  1. Clarke K, Zhong Q, Schwartz D, Coleman E, Kemppainen R, Judd R. Regulation of adiponectin secretion by endothelin-1. Biochem Biophys Res Commun. 2003;312:945-9 pubmed
    ..Our findings suggest vascular factors such as ET-1 may play a role in the regulation of adiponectin secretion and whole body energy metabolism. ..
  2. Yamashita T, Ohneda O, Nagano M, Iemitsu M, Makino Y, Tanaka H, et al. Abnormal heart development and lung remodeling in mice lacking the hypoxia-inducible factor-related basic helix-loop-helix PAS protein NEPAS. Mol Cell Biol. 2008;28:1285-97 pubmed
    ..The expression of endothelin 1 and platelet-derived growth factor beta was increased in the lung endothelial cells of NEPAS/HIF-3alpha-null ..
  3. Lund A, Agbor L, Zhang N, Baker A, Zhao H, Fink G, et al. Loss of the aryl hydrocarbon receptor induces hypoxemia, endothelin-1, and systemic hypertension at modest altitude. Hypertension. 2008;51:803-9 pubmed publisher
    ..Our studies establish the AHR KO mouse as a model in which modest decreases in PIO(2) lead to hypoxemia, increased plasma ET-1, and systemic hypertension without increased pulmonary prepro-ET-1 mRNA expression. ..
  4. Anggrahini D, Emoto N, Nakayama K, Widyantoro B, Adiarto S, Iwasa N, et al. Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation. Cardiovasc Res. 2009;82:143-51 pubmed publisher
    ..Furthermore, this study suggests a strategy for the efficient design of ET receptor antagonists with targeted inhibition of ET-1 signalling in vascular endothelial cells. ..
  5. Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, et al. Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest. 1995;96:293-300 pubmed
    ..To clarify the physiological and pathophysiological role of ET-1, we disrupted the mouse Edn1 locus encoding ET-1 by gene targeting and demonstrated that ET-1 is essential to the normal development of ..
  6. Adiarto S, Heiden S, Vignon Zellweger N, Nakayama K, Yagi K, Yanagisawa M, et al. ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci. 2012;91:651-7 pubmed publisher
    ..Endothelial ET-1 represents therefore a possible pharmacological target. ..
  7. Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, et al. Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature. 1994;368:703-10 pubmed
    ..These results suggest that ET-1 is essential for normal mouse development and may also play a physiological role in cardiovascular homeostasis...
  8. Kisanuki Y, Emoto N, Ohuchi T, Widyantoro B, Yagi K, Nakayama K, et al. Low blood pressure in endothelial cell-specific endothelin 1 knockout mice. Hypertension. 2010;56:121-8 pubmed publisher
    ..Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell-derived ET-1 acting on the vascular smooth muscle ET(A) receptor. ..
  9. Clouthier D, Hosoda K, Richardson J, Williams S, Yanagisawa H, Kuwaki T, et al. Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. Development. 1998;125:813-24 pubmed
    ..These observations define a novel genetic pathway for inductive communication between cephalic neural crest cells and their environmental counterparts. ..
  10. Ge Y, Ahn D, Stricklett P, Hughes A, Yanagisawa M, Verbalis J, et al. Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. Am J Physiol Renal Physiol. 2005;288:F912-20 pubmed
    ..These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD. ..

Detail Information

Publications96

  1. Clarke K, Zhong Q, Schwartz D, Coleman E, Kemppainen R, Judd R. Regulation of adiponectin secretion by endothelin-1. Biochem Biophys Res Commun. 2003;312:945-9 pubmed
    ..Our findings suggest vascular factors such as ET-1 may play a role in the regulation of adiponectin secretion and whole body energy metabolism. ..
  2. Yamashita T, Ohneda O, Nagano M, Iemitsu M, Makino Y, Tanaka H, et al. Abnormal heart development and lung remodeling in mice lacking the hypoxia-inducible factor-related basic helix-loop-helix PAS protein NEPAS. Mol Cell Biol. 2008;28:1285-97 pubmed
    ..The expression of endothelin 1 and platelet-derived growth factor beta was increased in the lung endothelial cells of NEPAS/HIF-3alpha-null ..
  3. Lund A, Agbor L, Zhang N, Baker A, Zhao H, Fink G, et al. Loss of the aryl hydrocarbon receptor induces hypoxemia, endothelin-1, and systemic hypertension at modest altitude. Hypertension. 2008;51:803-9 pubmed publisher
    ..Our studies establish the AHR KO mouse as a model in which modest decreases in PIO(2) lead to hypoxemia, increased plasma ET-1, and systemic hypertension without increased pulmonary prepro-ET-1 mRNA expression. ..
  4. Anggrahini D, Emoto N, Nakayama K, Widyantoro B, Adiarto S, Iwasa N, et al. Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation. Cardiovasc Res. 2009;82:143-51 pubmed publisher
    ..Furthermore, this study suggests a strategy for the efficient design of ET receptor antagonists with targeted inhibition of ET-1 signalling in vascular endothelial cells. ..
  5. Kurihara Y, Kurihara H, Oda H, Maemura K, Nagai R, Ishikawa T, et al. Aortic arch malformations and ventricular septal defect in mice deficient in endothelin-1. J Clin Invest. 1995;96:293-300 pubmed
    ..To clarify the physiological and pathophysiological role of ET-1, we disrupted the mouse Edn1 locus encoding ET-1 by gene targeting and demonstrated that ET-1 is essential to the normal development of ..
  6. Adiarto S, Heiden S, Vignon Zellweger N, Nakayama K, Yagi K, Yanagisawa M, et al. ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci. 2012;91:651-7 pubmed publisher
    ..Endothelial ET-1 represents therefore a possible pharmacological target. ..
  7. Kurihara Y, Kurihara H, Suzuki H, Kodama T, Maemura K, Nagai R, et al. Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature. 1994;368:703-10 pubmed
    ..These results suggest that ET-1 is essential for normal mouse development and may also play a physiological role in cardiovascular homeostasis...
  8. Kisanuki Y, Emoto N, Ohuchi T, Widyantoro B, Yagi K, Nakayama K, et al. Low blood pressure in endothelial cell-specific endothelin 1 knockout mice. Hypertension. 2010;56:121-8 pubmed publisher
    ..Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell-derived ET-1 acting on the vascular smooth muscle ET(A) receptor. ..
  9. Clouthier D, Hosoda K, Richardson J, Williams S, Yanagisawa H, Kuwaki T, et al. Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. Development. 1998;125:813-24 pubmed
    ..These observations define a novel genetic pathway for inductive communication between cephalic neural crest cells and their environmental counterparts. ..
  10. Ge Y, Ahn D, Stricklett P, Hughes A, Yanagisawa M, Verbalis J, et al. Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. Am J Physiol Renal Physiol. 2005;288:F912-20 pubmed
    ..These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD. ..
  11. Ahn D, Ge Y, Stricklett P, Gill P, Taylor D, Hughes A, et al. Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J Clin Invest. 2004;114:504-11 pubmed
    ..These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP. ..
  12. Shohet R, Kisanuki Y, Zhao X, Siddiquee Z, Franco F, Yanagisawa M. Mice with cardiomyocyte-specific disruption of the endothelin-1 gene are resistant to hyperthyroid cardiac hypertrophy. Proc Natl Acad Sci U S A. 2004;101:2088-93 pubmed
    b>Endothelin 1 (ET-1), a potent vasoconstrictor peptide expressed by endothelium, is also produced in the heart in response to a variety of stresses...
  13. Ho M, Lo A, Kurihara H, Yu A, Chung S, Chung S. Endothelin-1 protects astrocytes from hypoxic/ischemic injury. FASEB J. 2001;15:618-26 pubmed
    ..The present study suggests that astrocytes without ET-1 are more vulnerable to H and H/I injuries and that the up-regulation of astrocytic ET-1 is essential for the survival of astrocytes. ..
  14. Makita T, Sucov H, Gariepy C, Yanagisawa M, Ginty D. Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons. Nature. 2008;452:759-63 pubmed publisher
    ..Moreover, they suggest a model in which newborn sympathetic neurons distinguish and choose between distinct vascular trajectories to innervate their appropriate end organs. ..
  15. Nam J, Onitsuka I, Hatch J, Uchida Y, Ray S, Huang S, et al. Coronary veins determine the pattern of sympathetic innervation in the developing heart. Development. 2013;140:1475-85 pubmed publisher
    ..The proposed mechanism underlies a distinct, stereotypical pattern of autonomic innervation that is adapted to the complex tissue structure and physiology of the heart. ..
  16. Jin Y, Turcotte T, Crocker A, Han X, Yoon J. The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction. Dev Biol. 2011;352:1-13 pubmed publisher
    ..Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells...
  17. Widyantoro B, Emoto N, Nakayama K, Anggrahini D, Adiarto S, Iwasa N, et al. Endothelial cell-derived endothelin-1 promotes cardiac fibrosis in diabetic hearts through stimulation of endothelial-to-mesenchymal transition. Circulation. 2010;121:2407-18 pubmed publisher
    ..Targeting endothelial cell-derived ET-1 might be beneficial in the prevention of diabetic cardiomyopathy. ..
  18. Lee J, Yu Q, Shin J, Sebzda E, Bertozzi C, Chen M, et al. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev Cell. 2006;11:845-57 pubmed
    ..These findings identify Klf2 as an essential hemodynamic regulator in vivo and suggest that hemodynamic regulation in response to fluid shear stress is required for cardiovascular development and function. ..
  19. Zhao X, Pan W, Bekeredjian R, Shohet R. Endogenous endothelin-1 is required for cardiomyocyte survival in vivo. Circulation. 2006;114:830-7 pubmed
    ..This cardiac-protective effect is mediated by paracrine ET-1 modulation of TNF-related apoptosis, in part through upregulation of NF-kappaB signaling. ..
  20. Ieda M, Fukuda K, Hisaka Y, Kimura K, Kawaguchi H, Fujita J, et al. Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression. J Clin Invest. 2004;113:876-84 pubmed
    ..These findings indicate that endothelin-1 regulates NGF expression in cardiomyocytes and plays a critical role in sympathetic innervation of the heart. ..
  21. Trumpp A, Depew M, Rubenstein J, Bishop J, Martin G. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 1999;13:3136-48 pubmed
    ..Because the mutant mice resemble humans with first arch syndromes that include agnathia, our results raise the possibility that some of these syndromes are caused by mutations that affect FGF8 signaling in BA1 ectoderm...
  22. Leung J, Ho M, Lo A, Chung S, Chung S. Endothelial cell-specific over-expression of endothelin-1 leads to more severe cerebral damage following transient middle cerebral artery occlusion. J Cardiovasc Pharmacol. 2004;44 Suppl 1:S293-300 pubmed
    ..Our present TET model will serve as an ideal model for studying the role of endothelial ET- 1 in the pathogenesis of ischemic stroke. ..
  23. Olave N, Nicola T, Zhang W, Bulger A, James M, Oparil S, et al. Transforming growth factor-? regulates endothelin-1 signaling in the newborn mouse lung during hypoxia exposure. Am J Physiol Lung Cell Mol Physiol. 2012;302:L857-65 pubmed publisher
    ..ETAR blockade improves function but not development of the hypoxic newborn lung. Reduction of ET-1 via inhibition of TGF-? signaling indicates that TGF-? is upstream of ET-1 during hypoxia-induced signaling in the newborn lung. ..
  24. Sato T, Kurihara Y, Asai R, Kawamura Y, Tonami K, Uchijima Y, et al. An endothelin-1 switch specifies maxillomandibular identity. Proc Natl Acad Sci U S A. 2008;105:18806-11 pubmed publisher
    ..The endothelin-1 (Edn1)/endothelin receptor type-A (Ednra)-->Dlx5/6-->Hand2 signaling pathway is necessary for lower jaw formation...
  25. Wang W, Yen H, Yen H, Chen C, Soni R, Jasani N, et al. The endothelin-converting enzyme-1/endothelin-1 pathway plays a critical role in inflammation-associated premature delivery in a mouse model. Am J Pathol. 2008;173:1077-84 pubmed publisher
    ..The ability to control premature delivery by antagonizing or silencing the ECE-1/ET-1 system offers a novel approach to an unmet clinical need. ..
  26. Darwich R, Li W, Yamak A, Komati H, Andelfinger G, Sun K, et al. KLF13 is a genetic modifier of the Holt-Oram syndrome gene TBX5. Hum Mol Genet. 2017;26:942-954 pubmed publisher
    ..The data also suggest that, in human, KLF13 may be a genetic modifier of the Holt-Oram Syndrome gene TBX5. ..
  27. Hasue F, Kuwaki T, Kisanuki Y, Yanagisawa M, Moriya H, Fukuda Y, et al. Increased sensitivity to acute and persistent pain in neuron-specific endothelin-1 knockout mice. Neuroscience. 2005;130:349-58 pubmed
    ..The results of the present study suggest that neuronal ET-1 is involved in endogenous pain inhibitory control likely via pathways through the hypothalamus. ..
  28. Yanagisawa H, Hammer R, Richardson J, Williams S, Clouthier D, Yanagisawa M. Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice. J Clin Invest. 1998;102:22-33 pubmed
    ..This study demonstrates that ET-1/ETA-mediated signaling plays an essential role in a complex process of aortic arch patterning by affecting the postmigratory cardiac neural crest cell development. ..
  29. Ling G, Cao W, Onodera M, Ju K, Kurihara H, Kurihara Y, et al. Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice. Brain Res. 1998;808:238-49 pubmed
    ..Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice. ..
  30. Chang F, Flavahan S, Flavahan N. Immature endothelial cells initiate endothelin-mediated constriction of newborn arteries. J Physiol. 2016;594:4933-44 pubmed publisher
    ..Heightened activity of ET-1 in neonatal endothelium probably reflects an early developmental role of the peptide, although this might contribute to inappropriate responses of immature arteries to stress or injury. ..
  31. Sun Y, Teng I, Huo R, Rosenfeld M, Olson L, Li X, et al. Asymmetric requirement of surface epithelial ?-catenin during the upper and lower jaw development. Dev Dyn. 2012;241:663-74 pubmed publisher
    ..Changes in ?-catenin in vivo alter major epithelial Fgf8, Bmp4, Shh, and Edn1 signals, resulting in partial transcriptional reprogramming of the neural crest-derived mesenchyme, the primary ..
  32. Ni W, Zhan Y, He H, Maynard E, Balschi J, Oettgen P. Ets-1 is a critical transcriptional regulator of reactive oxygen species and p47(phox) gene expression in response to angiotensin II. Circ Res. 2007;101:985-94 pubmed
    ..In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47(phox). ..
  33. Vieux Rochas M, Mantero S, Heude E, Barbieri O, Astigiano S, Couly G, et al. Spatio-temporal dynamics of gene expression of the Edn1-Dlx5/6 pathway during development of the lower jaw. Genesis. 2010;48:262-373 pubmed publisher
    ..In particular, the endothelin-1 (Edn1)-dependent activation of Dlx5 and Dlx6 in CNCCs that colonize the first pharyngeal arch (PA1) is necessary and ..
  34. Thomas T, Kurihara H, Yamagishi H, Kurihara Y, Yazaki Y, Olson E, et al. A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development. 1998;125:3005-14 pubmed
    ..Mice harboring a null mutation of the endothelin-1 gene (Edn1), which is expressed in the epithelial layer of the branchial arches and encodes for the endothelin-1 (ET-1) ..
  35. Ivey K, Sutcliffe D, Richardson J, Clyman R, Garcia J, Srivastava D. Transcriptional regulation during development of the ductus arteriosus. Circ Res. 2008;103:388-95 pubmed publisher
  36. Wang X, Guo Z, Ding Z, Khaidakov M, Lin J, Xu Z, et al. Endothelin-1 upregulation mediates aging-related cardiac fibrosis. J Mol Cell Cardiol. 2015;80:101-9 pubmed publisher
    ..These observations in mice and human hearts suggest that aging-related cardiac fibrosis is, at least partially, dependent on the upregulation of ET-1. ..
  37. Lenoir O, Milon M, Virsolvy A, Henique C, Schmitt A, Masse J, et al. Direct action of endothelin-1 on podocytes promotes diabetic glomerulosclerosis. J Am Soc Nephrol. 2014;25:1050-62 pubmed publisher
    ..Furthermore, these results indicate that activation of the endothelin-1 pathways selectively in podocytes mediates pathophysiologic crosstalk that influences mesangial architecture and sclerosis. ..
  38. Saida K, Hashimoto M, Mitsui Y, Ishida N, Uchide T. The prepro vasoactive intestinal contractor (VIC)/endothelin-2 gene (EDN2): structure, evolution, production, and embryonic expression. Genomics. 2000;64:51-61 pubmed
    ..This study provides the basis for disruption and regulation analysis of the gene, which may lead to a better understanding of VIC/ET2's physiological significance. ..
  39. Zhou Q, Liu K, Wu H, Chen L, Pouranan V, Yuan M, et al. Spironolactone rescues Dot1a-Af9-mediated repression of endothelin-1 and improves kidney injury in streptozotocin-induced diabetic rats. PLoS ONE. 2012;7:e47360 pubmed publisher
    ..Therefore, Dot1a and Af9 as aldosterone-downregulated targets are negative regulators of endothelin-1 transcription in vitro and in vivo, and may be considered as new potential therapeutic targets of kidney injury in diabetes...
  40. Metz M, Lammel V, Gibbs B, Maurer M. Inflammatory murine skin responses to UV-B light are partially dependent on endothelin-1 and mast cells. Am J Pathol. 2006;169:815-22 pubmed
    ..This indicates that skin inflammation due to UV irradiation is caused in part by ET-1 acting on skin mast cells. ..
  41. Laumonnerie C, Bechara A, Vilain N, Kurihara Y, Kurihara H, Rijli F. Facial whisker pattern is not sufficient to instruct a whisker-related topographic map in the mouse somatosensory brainstem. Development. 2015;142:3704-12 pubmed publisher
    ..To investigate peripheral organisation in imposing a brain topographic pattern, we analysed Edn1(-/-) mice, which present ectopic whisker rows on the lower jaw...
  42. Martínez Miguel P, Medrano Andrés D, Griera Merino M, Ortiz A, Rodriguez Puyol M, Rodriguez Puyol D, et al. Tweak up-regulates endothelin-1 system in mouse and human endothelial cells. Cardiovasc Res. 2017;113:207-221 pubmed publisher
    ..Pharmacological blockade of this cytokine could prevent the haemodynamic and structural changes related to an increased ET-1 synthesis. ..
  43. Donato A, Lesniewski L, Stuart D, Walker A, Henson G, Sorensen L, et al. Smooth muscle specific disruption of the endothelin-A receptor in mice reduces arterial pressure, and vascular reactivity and affects vascular development. Life Sci. 2014;118:238-43 pubmed publisher
    ..Smooth muscle ETA is important for normal vascular, mandibular and thymic development and is involved in the maintenance of arterial pressure under physiological conditions. ..
  44. Zarpelon A, Pinto L, Cunha T, Vieira S, Carregaro V, Souza G, et al. Endothelin-1 induces neutrophil recruitment in adaptive inflammation via TNF? and CXCL1/CXCR2 in mice. Can J Physiol Pharmacol. 2012;90:187-99 pubmed publisher
    ..Therefore, the present study demonstrates that ET-1 is an important mediator for neutrophil recruitment in adaptive inflammation via TNF? and CXCL1/CXCR2-dependent mechanism. ..
  45. Nagase T, Kurihara H, Kurihara Y, Aoki Nagase T, Nagai R, Ouchi Y. Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice. J Appl Physiol (1985). 1999;87:2020-4 pubmed
    ..Recently, it has been reported that ET-1 and a gene encoding ET-1 (Edn1) might be involved in airway hyperresponsiveness, which is a major feature of bronchial asthma...
  46. Hammond T, Gadea A, Dupree J, Kerninon C, Nait Oumesmar B, Aguirre A, et al. Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron. 2014;81:588-602 pubmed publisher
    ..These findings reveal that ET-1 is a negative regulator of OPC differentiation and remyelination and is potentially a therapeutic target to promote lesion repair in demyelinated tissue. ..
  47. Tavares A, Clouthier D. Cre recombinase-regulated Endothelin1 transgenic mouse lines: novel tools for analysis of embryonic and adult disorders. Dev Biol. 2015;400:191-201 pubmed publisher
    Endothelin-1 (EDN1) influences both craniofacial and cardiovascular development and a number of adult physiological conditions by binding to one or both of the known endothelin receptors, thus initiating multiple signaling cascades...
  48. Manceau V, Kremmer E, Nabel E, Maucuer A. The protein kinase KIS impacts gene expression during development and fear conditioning in adult mice. PLoS ONE. 2012;7:e43946 pubmed publisher
    ..This difference suggests that disregulation of gene expression due to KIS inactivation affects specific brain functions. ..
  49. Tavares A, Garcia E, Kuhn K, Woods C, Williams T, Clouthier D. Ectodermal-derived Endothelin1 is required for patterning the distal and intermediate domains of the mouse mandibular arch. Dev Biol. 2012;371:47-56 pubmed publisher
    ..Endothelin-1 (Edn1)-induced signaling through the endothelin-A receptor (Ednra) is crucial for cranial NCC patterning within the ..
  50. Kuwaki T, Kurihara H, Cao W, Kurihara Y, Unekawa M, Yazaki Y, et al. Physiological role of brain endothelin in the central autonomic control: from neuron to knockout mouse. Prog Neurobiol. 1997;51:545-79 pubmed
    ..Definitive evidence is expected from thorough analyses of knockout mice by applying conventional experimental methods. ..
  51. Spinella F, Rosanò L, Di Castro V, Nicotra M, Natali P, Bagnato A. Endothelin-1 decreases gap junctional intercellular communication by inducing phosphorylation of connexin 43 in human ovarian carcinoma cells. J Biol Chem. 2003;278:41294-301 pubmed
  52. Ivey K, Tyson B, Ukidwe P, McFadden D, Levi G, Olson E, et al. Galphaq and Galpha11 proteins mediate endothelin-1 signaling in neural crest-derived pharyngeal arch mesenchyme. Dev Biol. 2003;255:230-7 pubmed
    ..We conclude that the Galpha(q) and Galpha(11) proteins serve as the intracellular mediators of ET-1 signaling in the pharyngeal arch mesenchyme. ..
  53. Buelli S, Rosanò L, Gagliardini E, Corna D, Longaretti L, Pezzotta A, et al. ?-arrestin-1 drives endothelin-1-mediated podocyte activation and sustains renal injury. J Am Soc Nephrol. 2014;25:523-33 pubmed publisher
  54. Sonveaux P, Dessy C, Martinive P, Havaux X, Jordan B, Gallez B, et al. Endothelin-1 is a critical mediator of myogenic tone in tumor arterioles: implications for cancer treatment. Cancer Res. 2004;64:3209-14 pubmed
    ..Thus, blocking the tumor-selective increase in the vascular endothelin-1/ETA pathway led us to unravel an important reserve of vasorelaxation that can be exploited to selectively increase tumor response to radiotherapy. ..
  55. Kozakai T, Sakate M, Masuo Y, Uchide T, Saida K. Increased gene expression of endothelin-1 and vasoactive intestinal contractor/endothelin-2 in the mammary gland of lactating mice. Biochem Biophys Res Commun. 2002;297:1339-43 pubmed
    ..The observed increase in ET-1 expression in differentiated epithelial cells suggests physiological roles for ET-1, including milk production and secretion in the mammary gland of lactating mice. ..
  56. Ong A. Surprising new roles for endothelins. BMJ. 1996;312:195-6 pubmed
  57. Herrera M, Hong N, Ortiz P, Garvin J. Endothelin-1 inhibits thick ascending limb transport via Akt-stimulated nitric oxide production. J Biol Chem. 2009;284:1454-60 pubmed publisher
    ..We conclude that endothelin-1 stimulates THAL NO production by activating PI3K, stimulating Akt activity, and phosphorylating NOS3 at Ser1177. This enhances NO production and inhibits sodium transport. ..
  58. Shin J, Salameh J, Richter J. Impaired neurodevelopment by the low complexity domain of CPEB4 reveals a convergent pathway with neurodegeneration. Sci Rep. 2016;6:29395 pubmed publisher
    ..Our study reveals a possible molecular convergence between a neurodevelopmental defect and neurodegeneration mediated by LCDs. ..
  59. Nishida T, Tsuji S, Kimura A, Tsujii M, Ishii S, Yoshio T, et al. Endothelin-1, an ulcer inducer, promotes gastric ulcer healing via mobilizing gastric myofibroblasts and stimulates production of stroma-derived factors. Am J Physiol Gastrointest Liver Physiol. 2006;290:G1041-50 pubmed
    ..Thus ET-1 has important roles not only in ulcer formation but also in ulcer healing via mobilizing myofibroblasts and inducing production of stroma-derived factors. ..
  60. Chang C, Pasolli H, Giannopoulou E, Guasch G, Gronostajski R, Elemento O, et al. NFIB is a governor of epithelial-melanocyte stem cell behaviour in a shared niche. Nature. 2013;495:98-102 pubmed publisher
    ..Our findings reveal how melanocyte and hair follicle stem cell behaviours maintain reliance upon cooperative factors within the niche, and how this can be uncoupled in injury, stress and disease states. ..
  61. Weinzierl M, Mautes A, Whetstone W, Lin Y, Noble Haeusslein L. Endothelin-mediated induction of heme oxygenase-1 in the spinal cord is attenuated in transgenic mice overexpressing superoxide dismutase. Brain Res. 2004;1030:125-32 pubmed
    ..Together, these findings suggest that ET-1 mediates oxidative stress in the spinal cord through the modulation of spinal cord blood flow. ..
  62. Yuyama H, Koakutsu A, Fujiyasu N, Fujimori A, Sato S, Shibasaki K, et al. Inhibitory effects of a selective endothelin-A receptor antagonist YM598 on endothelin-1-induced potentiation of nociception in formalin-induced and prostate cancer-induced pain models in mice. J Cardiovasc Pharmacol. 2004;44 Suppl 1:S479-82 pubmed
    ..These results suggest that selective endothelin-A receptor antagonists relieve pain in patients with various diseases in which ET-1 production increases (e.g. prostate cancer). ..
  63. Takuwa N, Takuwa Y, Yanagisawa M, Yamashita K, Masaki T. A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem. 1989;264:7856-61 pubmed
  64. Tanowitz H, Huang H, Jelicks L, Chandra M, Loredo M, Weiss L, et al. Role of endothelin 1 in the pathogenesis of chronic chagasic heart disease. Infect Immun. 2005;73:2496-503 pubmed
    On the basis of previous observations, endothelin 1 (ET-1) has been suggested as contributing to the pathogenesis of Chagasic cardiomyopathy...
  65. Yogi A, Callera G, Montezano A, Aranha A, Tostes R, Schiffrin E, et al. Endothelin-1, but not Ang II, activates MAP kinases through c-Src independent Ras-Raf dependent pathways in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2007;27:1960-7 pubmed
    ..These findings suggest that Ang II and ET-1 can activate similar signaling pathways through unrelated mechanisms. MAP kinases are an important point of convergence for Ang II and ET-1. ..
  66. Lu Y, Tsuprykov O, Vignon Zellweger N, Heiden S, Hocher B. Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice. Kidney Blood Press Res. 2016;41:770-780 pubmed publisher
    ..91). This meta-analysis provides robust evidence that global ET-1 overexpression in mice lowers blood pressure in an age-dependent manner. Older ET-1+/+ mice have a somewhat more pronounced reduction of blood pressure. ..
  67. Vignon Zellweger N, Relle K, Rahnenführer J, Schwab K, Hocher B, Theuring F. Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice. Life Sci. 2014;118:219-25 pubmed publisher
    ..Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases. ..
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    ..Here, we demonstrate that ROK increases actin polymerization, thus providing structural support for NFATc3 nuclear transport. ..
  69. Ortmann J, Nett P, Celeiro J, Traupe T, Tornillo L, Hofmann Lehmann R, et al. Endothelin inhibition delays onset of hyperglycemia and associated vascular injury in type I diabetes: evidence for endothelin release by pancreatic islet beta-cells. Biochem Biophys Res Commun. 2005;334:689-95 pubmed
    ..These data suggest a critical role for ET(A) receptor signaling in the development of autoimmune forms of diabetes and the early vascular injury associated with it. ..
  70. Gruber P, Epstein J. Development gone awry: congenital heart disease. Circ Res. 2004;94:273-83 pubmed
    ..In this review, we summarize some of the more clinically significant forms of congenital heart disease, and we highlight relevant genetic and developmental pathways. ..
  71. Liang J, Bi H, Ji W. Involvement of TRPA1 in ET-1-induced pain-like behavior in mice. Neuroreport. 2010;21:201-5 pubmed publisher
    ..Low dose of ET-1 could potentiate cinnamaldehyde-induced nociception. Our results suggested that TRPA1 is involved in ET-1-induced spontaneous pain-like behavior in mice. ..
  72. Shih M, Chen L, Cherng J. Chlorella 11-peptide inhibits the production of macrophage-induced adhesion molecules and reduces endothelin-1 expression and endothelial permeability. Mar Drugs. 2013;11:3861-74 pubmed publisher
    ..These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases. ..
  73. Bedi D, Clarke K, Dennis J, Zhong Q, Brunson B, Morrison E, et al. Endothelin-1 inhibits adiponectin secretion through a phosphatidylinositol 4,5-bisphosphate/actin-dependent mechanism. Biochem Biophys Res Commun. 2006;345:332-9 pubmed
    ..In conclusion, we demonstrate that ET-1 inhibits basal and insulin-stimulated adiponectin secretion through PIP(2) modulation of the actin cytoskeleton. ..
  74. Verri W, Cunha T, Parada C, Poole S, Liew F, Ferreira S, et al. Antigen-induced inflammatory mechanical hypernociception in mice is mediated by IL-18. Brain Behav Immun. 2007;21:535-43 pubmed
    ..Thus, IL-18 and IL-18-downstream mediators demonstrated herein might constitute targets to inhibit antigen-induced inflammatory pain. ..
  75. Wang Y, Cheng K, Lam K, Wu D, Wang Y, Huang Y, et al. APPL1 counteracts obesity-induced vascular insulin resistance and endothelial dysfunction by modulating the endothelial production of nitric oxide and endothelin-1 in mice. Diabetes. 2011;60:3044-54 pubmed publisher
    ..APPL1 plays a key role in coordinating the vasodilator and vasoconstrictor effects of insulin by modulating Akt-dependent NO production and ERK1/2-mediated ET-1 secretion in the endothelium. ..
  76. Ivins S, Lammerts van Beuren K, Roberts C, James C, Lindsay E, Baldini A, et al. Microarray analysis detects differentially expressed genes in the pharyngeal region of mice lacking Tbx1. Dev Biol. 2005;285:554-69 pubmed
    ..These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants. ..
  77. Liu Z, Li W, Ma X, Ding N, Spallotta F, Southon E, et al. Essential role of the zinc finger transcription factor Casz1 for mammalian cardiac morphogenesis and development. J Biol Chem. 2014;289:29801-16 pubmed publisher
    ..This suggests that CASZ1 is a novel 1p36 CHD gene and that the abnormal expression of cardiac morphogenesis and contraction genes induced by loss of Casz1 contributes to the heart defect. ..
  78. Chiu J, Xu B, Chen S, Feng B, Chakrabarti S. Oxidative stress-induced, poly(ADP-ribose) polymerase-dependent upregulation of ET-1 expression in chronic diabetic complications. Can J Physiol Pharmacol. 2008;86:365-72 pubmed publisher
    ..Hence, blockade of such pathways may constitute potential adjuvant treatment modalities in chronic diabetic complications. ..
  79. Tsang M, Lo A, Chan T, Chung S, Chung S. Expression of a neuropeptide, endothelin-1 in pons and medulla of prenatal and perinatal mouse brains. Int J Neurosci. 2005;115:1485-501 pubmed
    ..5 to D0.5), implicating the important role of ET-1 in central cardiorespiratory control regulating the onset of respiration during this critical period. ..
  80. Freeman B, Martins Y, Akide Ndunge O, Bruno F, Wang H, Tanowitz H, et al. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria. PLoS Pathog. 2016;12:e1005477 pubmed publisher
    ..This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria. ..
  81. Son G, Bak E, Kim J, Lee D, Kang S, Lee S, et al. Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. PLoS ONE. 2016;11:e0167713 pubmed publisher
    ..These results suggest that endothelin plays an important role in P. gingivalis-mediated periodontitis. Thus, endothelin antagonism may be a potential therapeutic approach for periodontitis treatment. ..
  82. Kuwaki T, Cao W, Kurihara Y, Kurihara H, Ling G, Onodera M, et al. Impaired ventilatory responses to hypoxia and hypercapnia in mutant mice deficient in endothelin-1. Am J Physiol. 1996;270:R1279-86 pubmed
    ..Our results demonstrate that ventilatory responses to hypoxia and hypercapnia are impaired in ET-1-deficient mice and suggest that endogenous ET-1 participates in the physiological control of ventilation...
  83. Reid K, Turnley A, Maxwell G, Kurihara Y, Kurihara H, Bartlett P, et al. Multiple roles for endothelin in melanocyte development: regulation of progenitor number and stimulation of differentiation. Development. 1996;122:3911-9 pubmed
    ..These findings indicate two key roles for endothelin in melanocyte development: regulation of expansion of the progenitor pool and differentiation of progenitors into mature melanocytes. ..
  84. Ambalavanan N, Li P, Bulger A, Murphy Ullrich J, Oparil S, Chen Y. Endothelin-1 mediates hypoxia-induced increases in vascular collagen in the newborn mouse lung. Pediatr Res. 2007;61:559-64 pubmed
    ..ET-AR blockade reduces collagen fiber area but not mRNA, and does not decrease elastin despite reducing its expression. ..
  85. Tokuda H, Hanai Y, Matsushima Nishiwaki R, Yamauchi J, Doi T, Harada A, et al. Rho-kinase regulates endothelin-1-stimulated IL-6 synthesis via p38 MAP kinase in osteoblasts. Biochem Biophys Res Commun. 2007;362:799-804 pubmed
    ..These results strongly suggest that Rho-kinase regulates ET-1-stimulated IL-6 synthesis through p38 MAP kinase activation in osteoblasts. ..
  86. Nagase T, Kurihara H, Kurihara Y, Aoki T, Fukuchi Y, Yazaki Y, et al. Airway hyperresponsiveness to methacholine in mutant mice deficient in endothelin-1. Am J Respir Crit Care Med. 1998;157:560-4 pubmed
    ..In mice, ET-1 as well as NO may have a significant role in the homeostasis of airway physiology. ..
  87. Kawamura K, Ye Y, Liang C, Kawamura N, Gelpke M, Rauch R, et al. Paracrine regulation of the resumption of oocyte meiosis by endothelin-1. Dev Biol. 2009;327:62-70 pubmed publisher
  88. Lagerqvist E, Finnin B, Pouton C, Haynes J. Endothelin-1 and angiotensin II modulate rate and contraction amplitude in a subpopulation of mouse embryonic stem cell-derived cardiomyocyte-containing bodies. Stem Cell Res. 2011;6:23-33 pubmed publisher
    ..These results indicate the presence of functional ET(A) and both AT? and AT? receptors in murine ESC-CMs, but their expression and or activity appears to be evident only in a limited set of BBs. ..
  89. Richard V, Solans V, Favre J, Henry J, Lallemand F, Thuillez C, et al. Role of endogenous endothelin in endothelial dysfunction in murine model of systemic sclerosis: tight skin mice 1. Fundam Clin Pharmacol. 2008;22:649-55 pubmed publisher
    ..The ET antagonist bosentan prevents endothelial alterations, suggesting a major role of ET in the adverse vascular effects of SSc. ..
  90. Talati M, West J, Blackwell T, Loyd J, Meyrick B. BMPR2 mutation alters the lung macrophage endothelin-1 cascade in a mouse model and patients with heritable pulmonary artery hypertension. Am J Physiol Lung Cell Mol Physiol. 2010;299:L363-73 pubmed publisher
    ..This is the first description of protein expression that distinguishes HPAH from IPAH in patients. ..