期刊
JOURNAL OF INFLAMMATION-LONDON
卷 19, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12950-021-00298-0
关键词
Inflammation; Colitis; TRIP6; TRAF6 signaling; Animal model
类别
资金
- Natural Science Foundation of Jiangsu Province [BK20190042, BK20181434, BK20190182, BK20200205]
- National Natural Science Foundation of China [82022050, 81972601, 81772541, 82002520]
- Science and Technology Foundation of Suzhou [SYS2019034]
- Fujian Provincial Key Laboratory of Innovative Drug Target Research
- Tang Scholar Funds
- Priority Academic Program Development of Jiangsu Higher Education Institutions
TRIP6, a member of the zyxin family, serves as an adaptor protein to regulate various biological processes. Through interactions with TRAF6, it is shown to play a positive regulatory role in DSS-induced colitis, activating inflammatory TRAF6 signaling.
Background TRIP6 is a zyxin family member that serves as an adaptor protein to regulate diverse biological processes. In prior reports, TRIP6 was shown to play a role in regulating inflammation. However, its in vivo roles and mechanistic importance in colitis remain largely elusive. Herein, we therefore employed TRIP6-deficient (TRIP6(-/-)) mice in order to explore the mechanistic importance of TRIP6 in a dextran sodium sulfate (DSS)-induced model of murine colitis. Findings Wild-type (TRIP6(+/+)) mice developed more severe colitis following DSS-mediated disease induction relative to TRIP6(-/-) mice, as evidenced by more severe colonic inflammation and associated crypt damage. TRIP6 expression in wild-type mice was significantly elevated following DSS treatment. Mechanistically, TRIP6 binds to TRAF6 and enhances oligomerization and autoubiquitination of TRAF6. This leads to the activation of NF-kappa B signaling and the expression of pro-inflammatory cytokines such as TNF alpha and IL-6, in the in vivo mouse model of colitis. Conclusions These in vivo data demonstrate that TRIP6 serves as a positive regulator of DSS-induced colitis through interactions with TRAF6 resulting in the activation of inflammatory TRAF6 signaling, highlighting its therapeutic promise as a protein that theoretically can be targeted to prevent or treat colitis.
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