SHP ‐1 ameliorates nonalcoholic steatohepatitis by inhibiting proinflammatory cytokine production

AbstractInflammation 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 (Ptpn6HKO) 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 (MCD) diet‐induced NASH model. Compared with the control littermates,Ptpn6HKO 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.

Source: FEBS Letters - July 2, 2020 Category: Biochemistry Authors: Lin Lin, Jie Jian, Chun ‐Yan Song, Fei Chen, Kai Ding, Wei‐Fen Xie, Ping‐Fang Hu Tags: RESEARCH ARTICLES Source Type: research