Investigation of the Expression Pattern and Functional Role of miR-10b in Intestinal Inflammation

Abstract

Implications of miRNAs for animal health management in livestock remain elusive. To identify suitable miRNAs as monitoring biomarkers, piglets were randomly selected for sampling on days 0, 1, 3, 7, and 14 post-weaning. The results show that miR-10b levels in the villus upper cells of the jejunum on days 3 and 7 were significantly lower than that on day 14 post-weaning and reduced by approximately 30% on day 3 and 55% on day 7 compared to day 0. In contrast, miR-10b in crypt cells decreased by approximately 82% on day 7 and 64% on day 14 compared with day 0. Next, miR-10 knockout mice and wild-type mice were subjected to dextran sulfate sodium (DSS) for 7 days. The findings demonstrate that mice lacking miR-10b were more susceptible to DSS administration, as demonstrated by worse survival, greater weight loss, more severe tissue damage, and increased intestinal permeability. Moreover, the increased disease severity was correlated with enhanced macrophage infiltration, coincident with significantly elevated pro-inflammatory mediators and immunoglobulins. Bioinformatic analysis further reveals that the enriched pathways were mainly involved in host immune responses, and Igtp was identified as a potential target of miR-10b. These findings may provide new strategies for future interventions for swine health and production.

miR‐10b‐5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes

“…Moreover, the study found that miR-10b deficiency exacerbated the immune response, including infiltration of macrophages and Ly6G þ neutrophils in colon tissue, elevated serum levels of LPS, DAO, D-LA, TNF-α, IL-1β, IFN-γ, IgM, IgA, and IgG in mir-10b KO mice after DSS treatment. 54 We confirmed the elevated TNF-α expression in mir-10b KO mice compared to WT. These findings, together with our study, suggest that miR-10b deficiency leads to intestinal permeability, dysregulation of tight junctions, and gut immune dysfunction.…”

“…A recent study demonstrated that deficiency of miR-10b increased susceptibility to DSS-induced colitis. 54 This study also revealed increased intestinal permeability in mir-10b KO mice after DSS treatment.…”

“…A recent study demonstrated that deficiency of miR‐10b increased susceptibility to DSS‐induced colitis. 54 This study also revealed increased intestinal permeability in mir‐10b KO mice after DSS treatment. Moreover, the study found that miR‐10b deficiency exacerbated the immune response, including infiltration of macrophages and Ly6G + neutrophils in colon tissue, elevated serum levels of LPS, DAO, D‐LA, TNF‐α, IL‐1β, IFN‐γ, IgM, IgA, and IgG in mir‐10b KO mice after DSS treatment.…”

Expression Profile of miR-199a and Its Role in the Regulation of Intestinal Inflammation

“…In contrast, miR-199a-3p was down-regulated in both jejunal villus cells and crypt cells on day 7 after weaning. These findings were consistent with our previous report, which demonstrated that miR-10b, another member of the miRNA family, had a decreased expression after weaning [24]. Moreover, both miR-199a-5p and miR-199a-3p were found to be differently expressed along the villus-crypt axis, which agreed with a previous study demonstrating that miR-199a-5p and -3p were up-regulated in jejunal villus cells as compared with crypt epithelial cells [21].…”

“…Gene Ontology (GO) analysis was performed using Goatools with Bonferroni-corrected p < 0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome were carried out by Metascape (v3.5.20230501) (https://metascape.org/, accessed on 3 May 2023) as previously described [24]. Prediction of target genes of miR-199a-5p or -3p was performed by StarBase v2.0 (https://starbase.sysu.edu.cn, accessed on 1 May 2023).…”