miR-379-5P INHIBITION ENHANCES INTESTINAL EPITHELIAL PROLIFERATION AND BARRIER FUNCTION RECOVERY AFTER ISCHEMIA/REPERFUSION BY TARGETING EIF4G2

Abstract

Gut barrier dysfunction caused by intestinal ischemia/reperfusion (I/R) injury is associated with substantial death and morbidity. In this research, the role of microRNAs (miRNAs) in regulating intestinal I/R injury was investigated. We used miRNA sequencing to analyze clinical ischemic and normal intestinal samples. Through bioinformatics analysis based on sequencing results, we found that upregulated miRNAs inhibited epithelial barrier function and cell proliferation, with miR-379-5p being the most significantly upregulated in the ischemic intestine. Further studies confirmed the role of miR-379-5p through experiments in the human ischemic intestine, the mouse I/R injury model in vivo, and cell hypoxia/reoxygenation models in vitro. Inhibiting miR-379-5p increased epithelial cell proliferation and improved barrier function after I/R injury. We also identified eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) as a downstream target gene of miR-379-5p through bioinformatics prediction and experimental verification. The findings suggest that inhibiting miR-379-5p could improve intestinal epithelial cell proliferation and barrier function by targeting EIF4G2. The goal of this study was to find a potential target for treating I/R injury in the intestine, as well as to prevent and mitigate the damage caused.

miR-329b-5p Affects Sheep Intestinal Epithelial Cells against Escherichia coli F17 Infection

“…miR-138-5p overexpression inhibits pyroptosis, promotes tight junctions, and ameliorates intestinal barrier breakdown [52]. Inhibition of miR-379-5p promotes IEC's proliferation, restores barrier function, and improves survival after intestinal injury [53]. This is consistent with the current study's results, which found that inhibition of miR-329b-5p promotes the proliferation of IECs, which are important for the stability of the intestinal barrier, based on CCK-8, EDU.…”

Unveiling the molecular complexity of intestinal ischemia–reperfusion injury through omics technologies

“…Another set of studies employed omics technologies to analyze intestinal tissues obtained from patients afflicted by intestinal IR injury caused by MA embolism or thrombosis, or by venous congestion or incarceration [47][48][49].…”

“…Five articles reported on the application of transcriptomics in human studies on intestinal IR [20,45,47,49,50] (Table 1, part II), of which two made use of the human experimental model [45,50]. Kip et al…”

“…Three articles reported on transcriptome data of intestinal tissue of patients suffering from intestinal IR [20,47,49]. The primary investigation was conducted by Jiang et al, encompassing a cohort of eight patients, of which five individuals exhibited arterial prob-lems, specifically embolism or thrombosis, while the remaining three were diagnosed with venous-related issues, such as congestion or incarceration [47].…”

“…The study of Jia et al focused on the identification of differentially expressed miRNA using miRNA-Seq analysis on intestinal tissue samples of three ischemic patients and three healthy controls [49]. Of all detected miRNAs, 11 were upregulated and seven were downregulated after intestinal ischemia.…”