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Effects and mechanism of adenovirus-mediated phosphatase and tension homologue deleted on chromosome ten gene on collagen deposition in rat liver fibrosis

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World Journal of Gastroenterology 2017年第32期23卷 5904-5912页

作者： Shu-rui Xie Jun-yan An Li-bo Zheng Xiao-Xia Huo Jian Guo David Shih Xiao-Lan Zhang Department of Gastroenterology The Second Hospital of Hebei Medical University Hebei Key Laboratory of Gastroenterology Hebei Institute of Gastro- enterology Department of Gastroenterology Xingtai People's Hospital Inflammatory Bowel and Immunobiology Research Institute F. Widjaja Foundation Cedars-Sinai Medical Center

AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(Pten) gene on collagen metabolism in hepatic fibrosis and the underlying *** rat primary hepatic stellate cells(HSCs) and human LX-2 cells were transfected with adenovirus containing c DNA constructs encoding wild-type Pten(Ad-Pten), Pten mutant G129 E gene(Ad-G129E), and r NA interference constructs targeting the Pten sequence Pten short hairpin r NA to up-regulate and downregulate the expression of Pten. HSCs were assayed using fluorescent microscopy, real-time polymerase chain reaction, and western blotting. Moreover, a CCl_4-induced rat hepatic fibrosis model was established to investigate the in vivo effects. Hematoxylin and eosin, and Masson's trichrome were used to assess the histological changes. The expression of collagen Ⅰ and Ⅲ was assessed using immunohistochemistry and western blot *** Elevated expression of Pten gene reduced serum levels of alanine transaminase and aspartate transaminase, decreased collagen deposition in the liver, and reduced hepatocyte necrosis. In contrast, knockdown of Pten expression had an opposite effect, such as increased collagen deposition in the liver, and was molecularly characterized by the increased expression of matrix metalloproteinase(MMP)-13(P ten might be a novel way of treating hepatic fibrosis.

关键词： Collagen metabolism Hepatic stellate cells phosphatase and tension homologue deleted on chromosome ten Pten Gene therapy Hepatic fibrosis

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