Products Cited in Publications Worldwide VANGL2 alleviates inflammatory bowel disease by recruiting the ubiquitin ligase MARCH8 to limit NLRP3 inflammasome activation through OPTN-mediated selective autophagy

VANGL2 alleviates inflammatory bowel disease by recruiting the ubiquitin ligase MARCH8 to limit NLRP3 inflammasome activation through OPTN-mediated selective autophagy

Jiang, Huaji; Xie, Yingchao; Hu, Zhiqiang; Lu, Jiansen; Zhang, Jiahuan; Li, Hongyu; Zeng, Ke; Peng, Wenqiang; Yang, Cheng; Huang, Junsheng

DOI: PMID:

Abstract

Inflammatory bowel disease (IBD) is a chronic and potentially life-threatening inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation, but the underlying mechanisms remain elusive. Here, we explore the role and precise mechanism of VanGogh-like 2 (VANGL2) during the pathogenesis of IBD. VANGL2 decreases in IBD patients and dextran sulfate sodium (DSS)-induced colitis in mice. Myeloid VANGL2 deficiency exacerbates the progression of DSS-induced colitis in mice and specifically enhances the activation of NLRP3 inflammasome in macrophages. NLRP3-specific inhibitor effectively alleviates DSS-induced colitis in VANGL2 deficient mice. Mechanistically, VANGL2 interacts with NLRP3 and promotes the autophagic degradation of NLRP3 through enhancing the K27-linked polyubiquitination at lysine 823 of NLRP3 by recruiting E3 ligase MARCH8, leading to optineurin (OPTN)-mediated selective . Notably, decreased VANGL2 in the peripheral blood mononuclear cells from IBD patients results in overt NLRP3 inflammasome activation and sustained inflammation. Taken together, this study demonstrates that VANGL2 acts as a repressor of IBD progression by inhibiting NLRP3 inflammasome activation and provides insights into the crosstalk between inflammation and in preventing IBD.

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MG-132

A181909133407-82-698%

MG-132

191.0/50mg

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