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TRIP6 promotes inflammatory damage via the activation of TRAF6 signaling in a murine model of DSS-induced colitis.

ABSTRACT:

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-κB signaling and the expression of pro-inflammatory cytokines such as TNFα 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.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8725398 | biostudies-literature |

REPOSITORIES: biostudies-literature

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