Abstract
Mucosal healing comprises a key goal of ulcerative colitis (UC) treatment. Anterior gradient protein 2 (AGR2) plays an important role in maintaining intestinal homeostasis in UC. However, the role of AGR2 in the repair of mucosal injury is not yet clear. This study is aimed at investigating the expression of AGR2 in the intestinal tissues of children with UC and its role in repairing mucosal injury. Forty UC patients who were hospitalized in the Pediatric Gastroenterology Ward of Shengjing Hospital affiliated with China Medical University between July 1, 2013, and May 31, 2020, and 20 children who had normal colonoscopy results during the same period (control group) made up the study sample. The disease activity of UC was evaluated based on the pediatric ulcerative colitis activity index, and the ulcerative colitis endoscopic index was evaluated according to the Rachmilewitz score. Immunohistochemical staining was employed to examine the differences in AGR2 expression in the intestinal mucosa between groups. The protective effect of AGR2 in a model of tumor necrosis factor-alpha- (TNF-α-) induced intestinal mucosal barrier injury and the underlying molecular mechanism were explored through in vitro experiments. The results showed that compared with the normal control group, UC patients in the remission or active period had significantly higher expression of AGR2 in the intestine. AGR2 expression was positively correlated with Ki67, an intestinal epithelial cell proliferation marker, but negatively correlated with the degree of endoscopic mucosal injury. In an in vitro model, AGR2 overexpression promoted cell proliferation and migration and inhibited TNF-α-induced intestinal epithelial barrier damage by activating yes-associated protein (YAP). Collectively, our study suggests that AGR2 might serve as a valuable biomarker to help assess the condition and mucosal healing status of UC patients. In vitro, AGR2 promoted the repair of intestinal mucosal barrier injury by activating YAP.
Highlights
The intestinal epithelial barrier is continuously exposed to an environment consisting of commensal microorganisms, food antigens, and invading pathogens [1]
The results showed that the protective effect of Anterior gradient protein 2 (AGR2) on the intestinal barrier was significantly weakened after the addition of verteporfin, which manifested as increased cell membrane permeability, reduced cell proliferation, and a significantly decreased mucosal healing ability (Figures 3(c)–3(f))
The results of this study showed that the expression of AGR2 in intestinal mucosal epithelial cells was significantly higher in ulcerative colitis (UC) patients than in the normal control group
Summary
The intestinal epithelial barrier is continuously exposed to an environment consisting of commensal microorganisms, food antigens, and invading pathogens [1]. Defective functioning of the intestinal epithelial barrier will cause microbial translocation and infiltration of inflammatory factors, eventually leading to inflammatory bowel disease (IBD) [2, 3]. Mucosal healing is a key factor in promoting disease remission and prolonging nonoperative survival in IBD patients [4]. To restore the epithelial barrier and gastrointestinal function, a rapid and effective way of repairing mucosal damage is needed. The rapid proliferation of intestinal epithelial cells and migration of intestinal epithelial cells to the injured sites are considered the key factors that promote mucosal healing [5, 6]. A previous study conducted by our group has confirmed that AGR2 regulates the expression of tight junction proteins and inhibits inflammatory factor-mediated intestinal mucosal barrier injury [8]. By analyzing the relationship between AGR2 expression in the intestinal mucosa
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