Knockdown of TRIM8 alleviates dextran sulfate sodium-induced colitis in mice by inhibiting the NF-κB signaling pathway
Main Article Content
Keywords
inflammation, NF-κB, TRIM8, ulcerative colitis
Abstract
Background: Although TRIpartite Motif containing 8 (TRIM8) gene plays an important role in a number of biological processes, such as inflammation, its function and mechanism in ulcerative colitis (UC) remain unknown.
Methods: The UC model was established by feeding mice with 3.5% dextran sulfate sodium (DSS). The animals were divided into the following four groups: control group, DSS group, DSS+short hairpin (sh)-NC group, and DSS+sh-TRIM8 group. Changes in body weight and disease activity index (DAI) score of mice in all the groups were recorded for 7 days. The animals were executed at the end of the experiment, and the expression of TRIM8 in colon tissue was detected by polymerase chain reaction and Western blot assays. The length of colon was measured, and the histopathological changes in mice colon were examined by hematoxylin and eosin staining. The expression of pro-inflammatory factors in mice serum and colonic tissue homogenate was detected by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) pathway-related proteins in colonic tissues was detected by Western-blot analysis.
Results: TRIM8 was highly expressed in the colonic tissues of UC mice. Knockdown of TRIM8 improved DSS-induced weight loss, increased DAI score, shortened colon length, and alleviated colonic injury and inflammation in mice. Western-blot experiments showed that knockdown of TRIM8 inhibited DSS-induced phosphorylation of p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) protein but increased IκBα expression.
Conclusion: Knockdown of TRIM8 inhibits UC injury and inflammatory response caused by DSS. This could be related to the regulation of NF-κB signaling pathway by TRIM8 protein.
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