上睑下垂
粒体自噬
非酒精性脂肪肝
炎症体
化学
脂肪变性
脱氧胆酸
品脱1
肝损伤
生物化学
脂肪肝
药理学
胆汁酸
细胞生物学
生物
内科学
内分泌学
医学
自噬
细胞凋亡
受体
疾病
作者
Xuebin Gao,Yongdui Ruan,Xuan Zhu,Xiaozhuan Lin,Xin Yan,Xiang Li,Meiqing Mai,Honghui Guo
出处
期刊:Inflammation
[Springer Nature]
日期:2021-10-21
卷期号:45 (2): 639-650
被引量:15
标识
DOI:10.1007/s10753-021-01573-1
摘要
Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), which can lead to liver fibrosis and cirrhosis. Bile acid levels are correlated with markers of hepatic injury in NASH, suggesting a possible role for bile acids in the progression of NAFLD. Here, we examined the role of deoxycholic acid (DCA) in driving steatotic hepatocytes to pyroptosis, a pro-inflammatory form of programmed cell death. HepG2 cells were stimulated with odium oleate and sodium palmitate for modeling steatotic hepatocytes and then treated with DCA alone or in combination with a specific mitophagy agonist, carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Our results showed that DCA dose-dependently induced a pro-inflammatory response in steatotic hepatocytes but had no significant effect on lipid accumulation. Moreover, activation of the NLRP3 inflammasome and pyroptosis were triggered by DCA. Expression levels of the mitophagy markers PTEN-induced kinase 1 (PINK1) and E3 ubiquitin ligase Parkin were significantly diminished by DCA, whereas induction of mitophagy by CCCP prevented DCA-induced inflammatory response and restored the pyroptosis. Collectively, our data showed that DCA-induced pyroptosis involves the inhibition of PINK1-mediated mitophagy and the activation of the NLRP3 inflammasome. These findings provide insight into the association of DCA with mitophagy, pyroptosis, and inflammation in NASH.
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