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The aim of this study was to establish the Nano NiO\u2010induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor \u03b21 (TGF\u2010\u03b21) in Smad pathway activation, epithelial\u2010mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24\u2009mg\/kg Nano NiO by intratracheal instilling twice a week for 9\u2009weeks. HepG2 cells were treated with 100\u2009\u03bcg\/mL Nano NiO and TGF\u2010\u03b21 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col\u2010I) and Col\u2010III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF\u2010\u03b21, p\u2010Smad2, p\u2010Smad3, alpha\u2010smooth muscle actin (\u03b1\u2010SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E\u2010cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO\u2010triggered the abnormal expression of the abovementioned proteins were all alleviated by co\u2010treatment with SB431542, implying that TGF\u2010\u03b21\u2010mediated Smad pathway, EMT and MMP9\/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF\u2010\u03b21\u2010mediated Smad pathway activation, EMT occurrence, and ECM deposition.<\/jats:p>","DOI":"10.1002\/tox.22878","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T10:42:51Z","timestamp":1574073771000},"page":"419-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["TGF\u2010\u03b21 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro"],"prefix":"10.1002","volume":"35","author":[{"given":"Qiong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Public Health Lanzhou University  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhong","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health Lanzhou 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