Revitalizing gut barrier integrity: miR-192-5p's role in enhancing autophagy via Rictor in enteritis

Background: 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.

Methods: 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 employed.

Results: 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.

Conclusion: 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 enteritis patients.

Rictor; autophagy; enteritis; intestinal epithelial barrier; miR-192-5p.