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Previously, we delineated the critical role of the control of extracellular matrix (ECM) stiffening by the mechanosensitive microRNA-130\/301 family, as activated by the YAP\/TAZ co-transcription factors, in promoting pulmonary hypertension (PH). We hypothesized that similar mechanisms may dictate fibrosis in other tissue beds beyond the pulmonary vasculature. Employing an <jats:italic>in silico<\/jats:italic> combination of microRNA target prediction, transcriptomic analysis of 137 human diseases and physiologic states and advanced gene network modeling, we predicted the microRNA-130\/301 family as a master regulator of fibrotic pathways across a cohort of seemingly disparate diseases and conditions. In two such diseases (pulmonary fibrosis and liver fibrosis), inhibition of microRNA-130\/301 prevented the induction of ECM modification, YAP\/TAZ and downstream tissue fibrosis. Thus, mechanical forces act through a central feedback circuit between microRNA-130\/301 and YAP\/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states. Such re-conceptualization of interconnections based on shared systems of disease and non-disease gene networks may have broad implications for future convergent diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.1038\/srep18277","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T11:18:14Z","timestamp":1450178294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["A YAP\/TAZ-miR-130\/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions"],"prefix":"10.1038","volume":"5","author":[{"given":"Thomas","family":"Bertero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Cottrill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Annis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balkrishen","family":"Bhat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette R.","family":"Gochuico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Osorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Rosas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen J.","family":"Haley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen E.","family":"Corey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Nelson Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Y.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,12,15]]},"reference":[{"key":"BFsrep18277_CR1","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nrc2544","volume":"9","author":"DT Butcher","year":"2009","unstructured":"Butcher, D. 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