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Up-regulation of Sphingosine kinase 1 (SphK1) is involved in TGF-\u03b21-induced activation of hepatic stellate cells (HSCs) in liver fibrogenesis. However, the molecular mechanism of TGF-\u03b21 regulates SphK1 remains unclear. This study was designed to investigate the role of HuR in TGF-\u03b21-induced SphK1 expression and identify a new molecular mechanism in liver fibrogenensis. <jats:italic>In vivo<\/jats:italic>, HuR expression was increased, translocated to cytoplasm and bound to SphK1 mRNA in carbon tetrachloride- and bile duct ligation-induced mouse fibrotic liver. HuR mRNA expression had a positive correlation with mRNA expressions of SphK1 and fibrotic markers, \u03b1-smooth muscle actin (\u03b1-SMA) and Collagen \u03b11(I), respectively. <jats:italic>In vitro<\/jats:italic>, up-regulation of SphK1 and activation of HSCs stimulated by TGF-\u03b21 depended on HuR cytoplasmic accumulation. The effects of TGF-\u03b21 were diminished when HuR was silenced or HuR cytoplasmic translocation was blocked. Meanwhile, overexpression of HuR mimicked the effects of TGF-\u03b21. Furthermore, TGF-\u03b21 prolonged half-life of SphK1 mRNA by promoting its binding to HuR. Pharmacological or siRNA-induced SphK1 inhibition abrogated HuR-mediated HSC activation. In conclusion, our data suggested that HuR bound to SphK1 mRNA and played a crucial role in TGF-\u03b21-induced HSC activation.<\/jats:p>","DOI":"10.1038\/srep22141","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T10:21:09Z","timestamp":1456395669000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Essential Roles of RNA-binding Protein HuR in Activation of Hepatic Stellate Cells Induced by Transforming Growth Factor-\u03b21"],"prefix":"10.1038","volume":"6","author":[{"given":"Jingjing","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,25]]},"reference":[{"key":"BFsrep22141_CR1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller, R. & Brenner, D. 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