| Autor: |
Qiu P; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Zhou K; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Wang Y; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Chen X; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Xiao C; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Li W; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Chen Y; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Chang Y; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Liu J; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Zhou F; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Wang X; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Shang J; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Liu L; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China., Qiu Z; Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China. |
| Abstrakt: |
Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis. NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis. |
