| Literature DB >> 33692776 |
Yong Shi1,2,3,4,5, Wantong Su1,2,3,4,5, Lei Zhang1,2,3,4,5, Chengyu Shi1,2,3,4,5, Jinren Zhou1,2,3,4,5, Peng Wang1,2,3,4,5, Hao Wang1,2,3,4,5, Xiaoli Shi1,2,3,4,5, Song Wei1,2,3,4,5, Qi Wang1,2,3,4,5, Johan Auwerx6, Kristina Schoonjans6, Yue Yu1,2,3,4,5, Rui Pan1, Haoming Zhou1,2,3,4,5, Ling Lu1,2,3,4,5.
Abstract
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of liver metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) is a cell surface receptor that is involved in multiple metabolic pathways. However, the functions of TGR5 in regulating macrophage innate immune activation in NASH remain unclear. Here, we found that TGR5 expression was decreased in liver tissues from humans and mice with NASH. Compared to wild type (WT) mice, TGR5-knockout (TGR5-/-) mice exhibited exacerbated liver damage, increased levels of proinflammatory factors, and enhanced M1 macrophage polarization. Moreover, TGR5 deficiency facilitated M1 macrophage polarization by promoting NLRP3 inflammasome activation and caspase-1 cleavage. Taken together, our findings revealed that TGR5 signaling attenuated liver steatosis and inflammation and inhibited NLRP3-mediated M1 macrophage polarization in NASH.Entities:
Keywords: G protein-coupled bile acid receptor 1; NLRP3 inflammasome; inflammation; macrophages; nonalcoholic steatohepatitis
Year: 2021 PMID： 33692776 PMCID： PMC7937818 DOI： 10.3389/fimmu.2020.609060
Source DB: PubMed Journal: Front Immunol ISSN： 1664-3224 Impact factor: 7.561