HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis.

Ulcerative colitis (UC) has been identified as a severe inflammatory disease with significantly increased incidence across the world. The detailed role and mechanism of HOXD10 in UC remain unclear. In present study, we found that HOXD10 was lowly expressed in UC samples and was notably decreased by dextran sulfate sodium (DSS) administration. Overexpression of HOXD10 dramatically ameliorated DSS-induced UC symptoms, including the loss of weight, increased disease activity index values, and the shortened colon length. Additionally, terminal-deoxynucleoitidyl transferase mediated nick end labeling and immunohistochemistry staining assays showed that HOXD10 overexpression suppressed cell apoptosis and facilitated proliferation of colon tissues after DSS treatment. Moreover, HOXD10 overexpression obviously suppressed DSS-triggered inflammatory response by decreasing the expression level of TNF-α, IL-6, and IL-1β. Furthermore, overexpression of HOXD10 effectively restored the intestinal permeability, thereby alleviating DSS-induced intestinal barrier dysfunction. Mechanistic study demonstrated that HOXD10 significantly reduced the activities of Rho/ROCK/MMPs axis in colon tissues of mice with UC. In conclusion, this study revealed that HOXD10 might effectively improve DSS-induced UC symptoms by suppressing the activation of Rho/ROCK/MMPs pathway.