The Role Of Erbin In Ulcerative Colitis And Its Preliminary Molecular Mechanism

Ulcerative colitis is a nonspecific inflammatory disease, if not a good treatment can easily develop cancers; In recent years, the incidence of ulcerative colitis showed a gradual upward trend in our country, but its etiology and pathogenesis have not yet been clarified. This study was designed by the establishment and application of colitis mouse model to reveal Erbin and its molecular mechanism of enteritis. This study will provide new ideas and theoretical basis for prevention and treatment of ulcerative colitis.We first observed the expression of Erbin in intestinal tissue; Then, we successfully constructed mouse model of ulcerative colitis and repair by the method of dextran sulfate sodium(DSS) chemically induced, Combined with spontaneous chronic colitis in mice(IL-10 knockout mice) model to detect the expression of Erbin; At the same time, we examined the expression of Erbin in patients with ulcerative colitis intestinal lesions tissue specimens.Further, we have established a Erbin C- terminal PDZ domain mutant mice(Erbin △ c / △ c mice) of ulcerative colitis and repair model, application DSS chemically induced method, to observe Erbin effects in ulcerative colitis and repair, and to explore whether Erbin may be involved in the regulation of autophagy pathway in ulcerative colitis.The main results are:(1) X-gal staining showed that Erbin in the mouse small intestine and colorectal epithelial tissues have higher expression.(2) An evaluation index results of body weight of mouse, isolated colorectal form, colorectal weight, length and histopathology and five kinds of inflammatory cytokines(IL-1β, IL-6, IL-10, TNF-a, MCP-1) mRNA expression show that DSS chemical induction method can be successfully established mouse model of ulcerative colitis and repair; Western blotting and immunohistochemistry results showed Erbin expression is lower in the acute phase of ulcerative colitis in mice colorectal tissue than the control group, the expression in colorectal tissue repair phase of ulcerative colitis in mice is higher.(3) Compared with the control group of mice, Erbin C- terminal PDZ domain mutant mice(Erbin △ c / △ c mice) ulcerative colitis acute phase weight loss severe, weight slow recovery in restoration phase; Colorectal shorter length, increase the weight and increase the ratio of length and weight; Histology showed inflammation is broader, crypt damage is very serious; Inflammatory cytokines IL-10 in the acute phase of ulcerative colitis colorectal tissues is high.(4) immunohistochemical detection of human clinical ulcerative colitis specimens,found Erbin expression was significantly decreased in intestine of active ulcerative colitis(5) immunofluorescence and immunoblotting show LC3 expression is lower in the acute phase of ulcerative colitis in mice colorectal tissue than the control group, the expression in colorectal tissue repair phase of ulcerative colitis in mice is higher. Without any treatment of Erbin △ c / △ c mouse colorectal tissues LC3 protein expression was higher than the wild-type(Erbin + / +) mice; Whether it is the acute phase of ulcerative colitis and repair phase, LC3 expression in Erbin △ c / △ c mouse colorectal tissues were higher than Erbin + / + mice.Conclusion: Erbin in the intestinal epithelium is highly expressed; Missing Erbin PDZ domains promote the occurrence of ulcerative colitis; Missing Erbin PDZ domains promote autophagy, which may be an important mechanism for the Erbin to regulate ulcerative colitis.