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Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence <jats:italic>in vivo<\/jats:italic>. The aim of this study is to examine the effects of conditional deletion of <jats:italic>TSC1<\/jats:italic> in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed <jats:italic>TSC1<\/jats:italic> gene with mice harboring <jats:italic>Col1\u03b12<\/jats:italic>-Cre-ER(T) successfully generated progeny with a conditional knockout of <jats:italic>TSC1<\/jats:italic> (<jats:italic>TSC1<\/jats:italic> CKO) in collagen I expressing mesenchymal cells. <jats:italic>TSC1<\/jats:italic> CKO and WT mice were subjected to CCl<jats:sub>4<\/jats:sub>, oil or CCl<jats:sub>4<\/jats:sub>+ rapamycin treatment for 8 weeks. <jats:italic>TSC1<\/jats:italic> CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of <jats:italic>TSC1<\/jats:italic> in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated <jats:italic>TSC1<\/jats:italic> CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl<jats:sub>4<\/jats:sub>\u2212 induced liver fibrosis and the rapamycin prevent its occurance.<\/jats:p>","DOI":"10.1038\/srep36037","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T10:07:35Z","timestamp":1478513255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["mTOR Overactivation in Mesenchymal cells Aggravates CCl4\u2212 Induced liver Fibrosis"],"prefix":"10.1038","volume":"6","author":[{"given":"Lanlan","family":"Shan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunzhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqing","family":"Nai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanfu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,7]]},"reference":[{"key":"BFsrep36037_CR1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","volume":"6","author":"V Hernandez-Gea","year":"2011","unstructured":"Hernandez-Gea, V. & Friedman, S. 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