胰腺炎
急性胰腺炎
发病机制
受体
生物
细胞生物学
内科学
医学
免疫学
生物化学
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-02
卷期号:10 (5)
标识
DOI:10.1126/sciadv.adj0146
摘要
Acute pancreatitis (AP) is one of the most common gastrointestinal diseases. Bile acids (BAs) were proposed to be a cause of AP nearly 170 years ago, though the underlying mechanisms remain unclear. Here, we report that two G protein–coupled receptors, GPR39 and GHSR, mediated cellular responses to BAs. Our results revealed GPR39 as an evolutionarily conserved receptor for BAs, particularly 3-O-sulfated lithocholic acids. In cultured cell lines, GPR39 is sufficient for BA-induced Ca 2+ elevation. In pancreatic acinar cells, GPR39 mediated BA-induced Ca 2+ elevation and necrosis. Furthermore, AP induced by BAs was significantly reduced in GPR39 knockout mice. Our findings provide in vitro and in vivo evidence demonstrating that GPR39 is necessary and sufficient to mediate BA signaling, highlighting its involvement in biliary AP pathogenesis, and suggesting it as a promising therapeutic target for biliary AP.
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