期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.893426
关键词
heat shock transcription factor 2; mitophagy; intestinal epithelial cells; ulcerative colitis; pathogenesis
资金
- National Natural Science Foundation of China [U1802282, 81960108, 82170550, 82160107]
- Applied Basic Research Projects of Yunnan Province [2019FE001(036)]
- Medicine Leading Talent of Health and Family Planning Commission of Yunnan Province [L-201607]
- Yunnan Health Training Project of High Level Talents [H-2019050]
- Yunnan Ten Thousand Talents Plan Young & Elite Talents Project
This study reveals that the overactivation of NLRP3 inflammasome in intestinal epithelial cells (IECs) in ulcerative colitis (UC) can be inhibited by heat shock transcription factor 2 (HSF2) through promoting mitophagy, resulting in the reduction of inflammation.
The overactivation of NLRP3 inflammasome in intestinal epithelial cells (IECs) is among the important reasons for severe inflammation in ulcerative colitis (UC). We found that heat shock transcription factor 2 (HSF2), which is highly expressed in UC, could inhibit the activation of NLRP3 inflammasome and reduce IL-1 beta in IECs, but the mechanisms were still not clear. It has been reported that HSP72 regulated by HSF2 can enhance the mitophagy mediated by Parkin. The number of damaged mitochondria and the mitochondrial derived ROS (mtROS) can be reduced by mitophagy, which means the activity of NLRP3 inflammasome is inhibited. Therefore, we speculate that HSF2 might regulate the activation of NLRP3 inflammasome of IECs in UC through the mitophagy mediated by Parkin. This study proves that the number of damaged mitochondria in IECs, the level of mitophagy, and the level of ROS in intestinal mucosa are positively correlated with the severity of UC. In mice and cells, mitophagy was promoted by HSF2 through the PARL/PINK1/Parkin pathway. This study reveals the potential mechanisms of HSF2 decreasing mtROS of IECs in UC.
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