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The mechanical stretch downregulated SO<jats:sub>2<\/jats:sub>\/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-\u03b21 (TGF- \u03b21) expression and phosphorylation of Smad2\/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- \u03b21 expression and phosphorylation of Smad2\/3 induced by stretch. Mechanistically, SB431542, a TGF-\u03b21\/Smad2\/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO<jats:sub>2<\/jats:sub> content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO<jats:sub>2<\/jats:sub> derivatives inhibited activation of TGF- \u03b21\/Smad2\/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO<jats:sub>2<\/jats:sub>\/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-\u03b21\/Smad2\/3 pathway.<\/jats:p>","DOI":"10.1038\/srep21112","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T11:33:53Z","timestamp":1455622433000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mechanical stretching stimulates collagen synthesis via down-regulating SO2\/AAT1 pathway"],"prefix":"10.1038","volume":"6","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selena","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoshu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbao","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,16]]},"reference":[{"key":"BFsrep21112_CR1","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.pcad.2012.07.004","volume":"55","author":"EB Rosenzweig","year":"2012","unstructured":"Rosenzweig, E. 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