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Endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101) is primarily produced by vascular endothelial cells and plays multiple roles in the wound\u2010healing response and organ fibrogenesis. In this study, we investigated the pathophysiological significance of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 and involvement of RhoA, a member of the Rho <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ases, in hypertrophic scar\/keloid formation. We found that <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 expression on dermal microvascular endothelial cells (<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s) in hypertrophic scars and keloids was higher than that in normal skin and mature scars. We also confirmed that <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 induced myofibroblast differentiation and collagen synthesis in cultured human dermal fibroblasts through the RhoA\/Rho\u2010kinase pathway. Finally, since hypertrophic scar\/keloid formation was most prominent in areas exposed to mechanical stretch, we examined how mechanical stretch affected <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 secretion in human dermal microvascular <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s, and found that mechanical stretch increased <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 gene expression and secretion from <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s. Taken together, these results suggest that dermal microvascular <jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>s release <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 in response to mechanical stretch, and thereby contribute to the formation of hypertrophic scars and keloids through the RhoA\/Rho\u2010kinase pathway.<\/jats:p>","DOI":"10.1111\/exd.13264","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T12:52:43Z","timestamp":1480337563000},"page":"705-712","source":"Crossref","is-referenced-by-count":37,"title":["Endothelial cell\u2010derived endothelin\u20101 is involved in abnormal scar formation by dermal fibroblasts through RhoA\/Rho\u2010kinase pathway"],"prefix":"10.1111","volume":"26","author":[{"given":"Koichiro","family":"Kiya","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tateki","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Hyogo College of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Wakayama Medical University  Kimiidera Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Hyogo College of Medicine  Nishinomiya Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimitsu","family":"Nishibayashi","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Kanazawa","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genki","family":"Amano","sequence":"additional","affiliation":[{"name":"Department of Child Development and Molecular Brain Science United Graduate School of Child Development Osaka University  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiichi","family":"Katayama","sequence":"additional","affiliation":[{"name":"Department of Child Development and Molecular Brain Science United Graduate School of Child Development Osaka University  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Osaka University Graduate School of Medicine  Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm_00000231"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1427"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2008.08.007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/332411a0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50044"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.938217"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0175TR"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373425"},{"key":"e_1_2_9_10_1","first-page":"1268","volume":"21","author":"Vancheeswaran R.","year":"1994","journal-title":"J. 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