Revitalizing gut barrier integrity: role of miR-192-5p in enhancing autophagy via Rictor in enteritis.
Peishan QiuKezhi ZhouYouwei WangXiaoyu ChenCong XiaoWenjie LiYuhua ChenYing ChangJing LiuFeng ZhouXiaobing WangJian ShangLan LiuZhao QiuPublished in: American journal of physiology. Gastrointestinal and liver physiology (2024)
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.
Keyphrases
- oxidative stress
- cell death
- signaling pathway
- diabetic rats
- endoplasmic reticulum stress
- poor prognosis
- gene expression
- metabolic syndrome
- south africa
- high throughput
- real time pcr
- genome wide
- long non coding rna
- skeletal muscle
- cerebral ischemia
- dna methylation
- drug delivery
- copy number
- drug induced
- subarachnoid hemorrhage