Kupffer cell pyroptosis mediated by METTL3 contributes to the progression of alcoholic steatohepatitis.

Chronic alcohol consumption is a major risk factor for alcoholic steatohepatitis (ASH). Previous studies have shown that direct injury of hepatocytes is the key factor in its occurrence and development. However, our study shows that the role of Kupffer cells in ASH cannot be ignored. We isolated Kupffer cells from the livers of ASH mice and found that alcohol consumption induced Kupffer cell pyroptosis and increased the release of interleukin-1β (IL-1β). Furthermore, we screened the related m6A enzyme methyltransferase-like 3 (METTL3) from liver Kupffer cells, and found that silencing METTL3 alleviated inflammatory cytokine eruption by Kupffer cell pyroptosis in ASH mice. In vitro, we silenced METTL3 with lentivirus in BMDMs and RAW264.7 cells and confirmed that METTL3 could reduce pyroptosis by influencing the splicing of pri-miR-34A. Together, our results revealed a critical role of KC pyroptosis in ASH and highlighted the mechanism by which METLL3 relieves cell pyroptosis, which could be a promising therapeutic strategy for ASH. © 2023 Federation of American Societies for Experimental Biology.

Citation

Xue-Sheng Pan, Bo-Wen Li, Li-Li Wang, Ning Li, Hui-Min Lin, Jin Zhang, Na Du, Yue-Qin Zhu, Xian Wu, Cheng-Mu Hu, Wen-Yong Wu, Hui Hou, Hong-Chuan Zhao, Song-Yan Liao, Ya-Nan Yang, Yan Huang. Kupffer cell pyroptosis mediated by METTL3 contributes to the progression of alcoholic steatohepatitis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2023 Jun;37(6):e22965

Mesh Tags

Substances

PMID: 37171272

search → result