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Ubiquitin-specific protease 47 regulates intestinal inflammation through deubiquitination of TRAF6 in epithelial cells
- Source :
- Science China Life Sciences. 65:1624-1635
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
Abstract
- Deubiquitinates (DUBs) alter the stabilities, localizations or activities of substrates by removing their ubiquitin conjugates, which are closely related to the development of inflammatory response. Here, we show that ubiquitin-specific protease 47 (USP47) prevents inflammation development in inflammatory bowel disease (IBD). Compared with wild-type mice, Usp47 knockout mice are more susceptible to dextran sodium sulfate (DSS)-induced acute and chronic colitis with higher inflammatory cytokines expression and severe intestinal tissue damage. Chimeric mouse experiments suggest that non-hematopoietic cells mainly contribute to the phenotype. And, DSS-induced colitis of the Usp47 knockout mice depends on commensal bacteria. Mechanistically, down-regulation of USP47 aggravates the activation of NF-κB signaling pathway by increasing the K63-linked poly-ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) in intestinal epithelial cells. Furthermore, the expression of USP47, negatively correlated with the degree of inflammation, is lower at colonic inflammatory lesions than that non-inflammatory sites from the intestine from ulcerative colitis (UC) and Crohn's disease (CD) patients. These data, taken together, indicate that USP47 regulates intestinal inflammation through de-ubiquitination of K63-linked poly-ubiquitination TRAF6 in intestinal epithelial cells.
- Subjects :
- Inflammation
Mice, Inbred C57BL
Mice, Knockout
TNF Receptor-Associated Factor 6
Mice
Animals
Epithelial Cells
Ubiquitin-Specific Proteases
Intestinal Mucosa
Colitis
General Agricultural and Biological Sciences
General Biochemistry, Genetics and Molecular Biology
General Environmental Science
Subjects
Details
- ISSN :
- 18691889 and 16747305
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Science China Life Sciences
- Accession number :
- edsair.doi.dedup.....ffe90cf0055a4b055e43cbd91c7299da