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SHP‐1 ameliorates nonalcoholic steatohepatitis by inhibiting proinflammatory cytokine production
Author(s) -
Lin Lin,
Jian Jie,
Song ChunYan,
Chen Fei,
Ding Kai,
Xie WeiFen,
Hu PingFang
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13879
Subject(s) - proinflammatory cytokine , inflammation , steatosis , steatohepatitis , fibrosis , tumor necrosis factor alpha , medicine , endocrinology , biology , cancer research , fatty liver , disease
Inflammation is the main contributor for the pathogenesis of nonalcoholic steatohepatitis (NASH). Src homology region 2 domain‐containing phosphatase 1 (SHP‐1, also known as PTPN6) is regarded as a negative regulator of inflammation, but its role in NASH remains unknown. Here, hepatocyte‐specific Ptpn6 knockout mice ( Ptpn6 HKO ) and adenovirus vector‐mediated ectopic expression of SHP‐1 (AdSHP1) were used to evaluate the role of SHP‐1 in a methionine‐ and choline‐deficient diet‐induced NASH model. Compared with the control littermates, Ptpn6 HKO mice show exacerbated hepatic steatosis, inflammation, and fibrosis. Additionally, administration of AdSHP1 significantly ameliorates steatohepatitis and inhibits the expression of proinflammatory cytokines, including transforming growth factor‐β, interleukin‐6, and tumor necrosis factor‐α. Our data indicate that SHP‐1 could be a potential therapeutic target for NASH.