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 (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 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.

中文翻译：

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SHP-1 通过抑制促炎细胞因子的产生来改善非酒精性脂肪性肝炎

炎症是非酒精性脂肪性肝炎 (NASH) 发病机制的主要因素。Src 同源区 2 域含磷酸酶 1（SHP-1，也称为 PTPN6）被认为是炎症的负调节因子，但其在 NASH 中的作用尚不清楚。在这里，肝细胞特异性 Ptpn6 敲除小鼠 (Ptpn6HKO) 和腺病毒载体介导的 SHP-1 异位表达 (AdSHP1) 用于评估 SHP-1 在缺乏蛋氨酸和胆碱的饮食诱导的 NASH 模型中的作用。与对照同窝小鼠相比，Ptpn6HKO 小鼠的肝脂肪变性、炎症和纤维化加剧。此外，AdSHP1 的给药显着改善脂肪性肝炎并抑制促炎细胞因子的表达，包括转化生长因子-β、白细胞介素-6 和肿瘤坏死因子-α。