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前梯度蛋白 2 促进小儿溃疡性结肠炎的黏膜修复。

Anterior Gradient Protein 2 Promotes Mucosal Repair in Pediatric Ulcerative Colitis.

机构信息

Department of Gastroenterology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Department of Pediatrics, China Medical University Affiliated with Shengjing Hospital, Shenyang, 110004 Liaoning, China.

出版信息

Biomed Res Int. 2021 May 18;2021:6483860. doi: 10.1155/2021/6483860. eCollection 2021.

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--) induced intestinal mucosal barrier injury and the underlying molecular mechanism were explored through 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 model, AGR2 overexpression promoted cell proliferation and migration and inhibited TNF--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. , AGR2 promoted the repair of intestinal mucosal barrier injury by activating YAP.

摘要

黏膜愈合是溃疡性结肠炎 (UC) 治疗的关键目标。前沿梯度蛋白 2 (AGR2) 在维持 UC 肠道内稳态中发挥重要作用。然而,AGR2 在黏膜损伤修复中的作用尚不清楚。本研究旨在探讨 AGR2 在 UC 患儿肠组织中的表达及其在修复黏膜损伤中的作用。

本研究纳入了 2013 年 7 月 1 日至 2020 年 5 月 31 日期间在中国医科大学附属盛京医院儿科消化科住院的 40 例 UC 患儿(UC 组)和同期结肠镜检查结果正常的 20 例儿童(对照组)。根据小儿溃疡性结肠炎活动指数评估 UC 患儿的疾病活动度,根据 Rachmilewitz 评分评估溃疡性结肠炎内镜指数。采用免疫组织化学染色法检测两组患儿肠黏膜 AGR2 表达的差异。通过实验探讨 AGR2 在肿瘤坏死因子-α(TNF-)诱导的肠黏膜屏障损伤模型中的保护作用及其潜在的分子机制。

结果显示,与正常对照组相比,缓解期和活动期 UC 患儿肠组织中 AGR2 的表达明显升高。AGR2 表达与 Ki67(一种肠上皮细胞增殖标志物)呈正相关,与内镜黏膜损伤程度呈负相关。在 TNF-诱导的肠上皮屏障损伤模型中,AGR2 过表达通过激活 yes 相关蛋白(YAP)促进细胞增殖和迁移,抑制 TNF-诱导的肠上皮屏障损伤。

综上所述,本研究提示 AGR2 可能作为一种有价值的生物标志物,有助于评估 UC 患者的病情和黏膜愈合状态。此外,AGR2 通过激活 YAP 促进肠黏膜屏障损伤的修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85d8/8149229/21552ce99d05/BMRI2021-6483860.001.jpg

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