MiRNA-182-5p aggravates experimental ulcerative colitis via sponging Claudin-2

Abstract

Tight junction proteins play crucial roles in maintaining the integrity of intestinal mucosal barrier. MiRNA-182-5p is capable of targeting claudin-2 which is one of the vital tight junction proteins and the effect and mechanism of miRNA-182-5p was explored here in the DSS-induced colitis model. The pathological conditions were evaluated via hematoxylin and eosin staining. The gene expression level was assessed via PCR. Quantitative immunohistochemistry analysis was performed for the measurement of claudin-2. microRNA.org online tool was used for target gene prediction. Luciferase reporter assay and RNA pull-down assay were performed to detect the target of miRNA-182-5p. The inflammatory and oxidative stress level were measured using corresponding kits. MiRNA-182-5p was highly expressed in colitis model and miRNA-182-5p inhibitor exerted protective effects on colitis induced by DSS in mice. The protective effects includded improvement of pathological changes, increases in anti-inflammation and anti-oxidative genes, and up-regulation of TGF-β1. Claudin-2 mRNA was predicted as the target of miRNA-182-5p, which was validated via luciferase reporter assay and RNA pull-down assay. Claudin-2 overexpression was found in miRNA-182-5p inhibitor group. Consistent with the role of miRNA-182-5p, claudin-2 overexpression also exerted protective effects on DSS-induced colitis in mice. Inhibition of miRNA-182-5p exerted protective effects on colitis via targeting and upregulating claudin-2. The findings in study provide a new therapeutic strategy for colitis treatment and lay the foundation for future study.

Novel ginsenoside monomer RT4 promotes colitis repair in mice by regulating miR‐144‐3p/SLC7A11 signaling pathway

“…Certain miRNAs have been linked to the etiology of colitis. Several miRNAs, including miR‐182‐5p, miR‐31, miR‐223‐3p, and miR‐98‐5p, have been related with pathophysiology of colitis [18–21]. Ginsenoside RT4 blocked the activation of macrophages miR‐144‐3p/SLC7A11 signaling pathways in LPS‐stimulated inflammation in vitro and downregulated miR‐144‐3p/SLC7A11 signaling pathways in response to the recovery of 4‐day DSS‐induced colitis in vivo.…”

Anti-ulcerative colitis effects of chemically characterized extracts from Calliandra haematocephala in acetic acid-induced ulcerative colitis

“…The supernatant of colon tissue was used for the measurement of SOD using SOD assay kit according to the protocol given by the manufacturer ( Tang et al, 2021 ). Measurement of SOD activity was done to assess the functionality of the antioxidant defense system and the balance between oxidant and antioxidant mechanisms.…”

The Impact of MicroRNAs during Inflammatory Bowel Disease: Effects on the Mucus Layer and Intercellular Junctions for Gut Permeability

“…Moreover, miR-34 in combination with long non-coding RNA PlncRNA1 cooperatively regulated the expression of occludin and ZO1 in Caco-2 monolayers undergoing DSS-induced colitis [ 168 ]. Regarding relevant claudins, claudin-2 was recently demonstrated to be a target of miR-182-5p, whose inhibition led to increased claudin-2 and TGF-β1 expression, as well as anti-inflammatory and anti-oxidative genes [ 169 ]. The suppression of occludin and claudin-1 has been attributed to miR-874, while also targeted by miR-29b, which was shown to be sequestered via the addition of long non-coding RNA uc.173 as well as circular RNA CircHIPK3 [ 170 , 171 , 172 ], rescuing barrier function.…”