E3 ubiquitinase RNF138 inhibits the development of ulcerative colitis

Abstract

Objective To explore the role of RNF138 (ring finger protein 138) in the ulcerative colitis (UC). Methods The expression of RNF138 in active, remission and ulcerative colitis upon immunosuppressive treatment was analyzed by GEO database. The UC model was constructed by RNF138-deficient mice. The pathological observation, histological analysis and colon measurement were performed by the model mice. The transcriptome analysis was employed by using mouse colon tissue samples. The expression levels of RNF138 and p-p65 in colon tissue of model mice were detected by immunohistochemistry and Western blots. The expression of target gene of NF-кB pathway was detected by qPCR. Immunohistochemistry was used to evaluate the expression of RNF138 and NF-кB p65 in clinical samples of UC. Results GEO database and clinical samples showed that the expression of RNF138 decreased in the samples of active UC as compared to that in the remission stage(P＜0.05). Knocking out RNF138 promoted the occurrence and progression of DSS induced UC (P＜0.05). Knocking out RNF138 promoted upregulation of p-p65 and its target gene expression(P＜0.05), indicating NF-кB signal pathway activation. Conclusions RNF138 inhibits the development of UC through suppressing the NF-кB genetic pathway.

Keywords

• rnf138|ulcerative colitis|nf-кb