{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:13:44Z","timestamp":1768972424634,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T00:00:00Z","timestamp":1348185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 829 and KR558"],"award-info":[{"award-number":["SFB 829 and KR558"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mechanical forces are highly variable ranging from the ubiquitous gravity force to compression, fluid shear, torsion, tension and other forms. Mechanical forces act on cells and modulate their biological responses by regulating gene transcription, enzyme and growth factor activity. In soft connective tissues, formation of myofibroblasts strictly requires a mechanically loaded environment in addition to local transforming growth factor (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>)\u2010\u03b2 activity, which itself can be modulated by the mechanical status of the environment. The aim of this study was to monitor the adaptive responses of primary dermal fibroblasts towards cyclic mechanical stress under conditions of high force to better understand the regulation of gene expression in normal skin and mechanisms of gene regulation in mechanically altered fibrotic skin. Primary murine dermal fibroblasts were exposed to equi\u2010biaxial tensile strain. Cyclic mechanical tension was applied at a frequency of 0.1\u00a0<jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>z (6\u00d7\u00a0\/min) for 24\u00a0h with a maximal increase in surface area of 15%. This treatment resulted in downregulation of alpha smooth muscle actin (\u03b1<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>) and connective tissue growth factor (<jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>) but not of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b21 expression. Cyclic strain also strongly reduced endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101) expression and supplementing strained cultures with exogenous <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 rescued \u03b1<jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content> levels. Of note, no biologically significant levels of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b21 activity were detected in strained cultures. We provide evidence for a novel, <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b21\u2010independent mechanism regulating <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 expression in dermal fibroblasts by biomechanical forces. Modulation of <jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101\u2010dependent activities regulates downstream fibrotic marker genes; this pathway might therefore provide an approach to attenuate myofibroblast differentiation.<\/jats:p>","DOI":"10.1111\/exd.12010","type":"journal-article","created":{"date-parts":[[2012,8,20]],"date-time":"2012-08-20T08:33:08Z","timestamp":1345451588000},"page":"765-770","source":"Crossref","is-referenced-by-count":13,"title":["Cyclic mechanical stress downregulates endothelin\u20101 and its responsive genes independently of <scp>TGF<\/scp>\u03b21 in dermal fibroblasts"],"prefix":"10.1111","volume":"21","author":[{"given":"Andreas S.","family":"Peters","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Brunner","sequence":"additional","affiliation":[{"name":"Cancer Research, Fachklinik Hornheide M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrin","family":"Blumbach","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Abraham","sequence":"additional","affiliation":[{"name":"Center for Rheumatology University College London (Royal Free Campus) London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Krieg","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) Cologne Germany"},{"name":"Center for Molecular Medicine (CMMC) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Eckes","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,9,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.041105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(99)00039-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.12.025"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq143"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.08.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04695"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.027"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0806188"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31139"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.144.5.666"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005066"},{"key":"e_1_2_8_13_1","first-page":"70","volume":"5","author":"Wall 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