miR‐223 improves intestinal inflammation through inhibiting the IL‐6/STAT3 signaling pathway in dextran sodium sulfate‐induced experimental colitis

Abstract

Introduction The pathogenesis of inflammatory bowel disease (IBD) has not yet been clarified and is closely related to several pro‐inflammatory factors. MicroRNA‐233 (miR‐223) might be involved in the development of IBD; however, the mechanism underlying its pathogenesis is unclear. In this study, we attempted to determine the role of miR‐223 in dextran sodium sulfate (DSS)‐induced colitis and explore the involvement of the IL‐6/STAT3 pathway in the development of intestinal mucosal inflammation. Materials and Methods Except control (WT) group, male C57BL/6 mice were provided DSS, then treated for with miR‐223 agomir or antagomir including DSS group, DSS + miR‐223 agomir (DSS + A) group, and DSS + miR‐223 antagomir (DSS + AN) group. The colitis symptoms were observed, the disease activity index (DAI) score were recorded daily, and colonic inflammation was evaluated by histopathological scoring. The expression of myeloperoxidase (MPO), cytokines and IL‐6/STAT3 pathway‐related proteins were measured. Results miR‐223 expression in the terminal ileum and colon was increased in the DSS group compared with the WT group. Colitis symptoms were significantly alleviated in the DSS + A group and exacerbated in the DSS + AN group after administration of the miR‐223 agomir and antagomir, respectively. MPO, tumor necrosis factor‐α, IL‐6, and IL‐17 were decreased and IL‐10 was increased in the DSS + A group, but these changes were reversed in the DSS + AN group. Gp130, p‐STAT3, Bcl‐2, and Bcl‐xl in the colon declined in the DSS + A group, but these levels increased in the DSS + AN group. Conclusions The upregulation of miR‐223 by agomir administration alleviated colonic inflammation in a DSS‐induced colitis model, which was likely mediated by inhibiting the production of pro‐inflammatory cytokines via the IL‐6/STAT3 signaling pathway. These findings provide evidence that miR‐223 might have potential therapeutic implications in IBD.

Transcriptional Network Analysis Reveals the Role of miR-223-5p During Diabetic Corneal Epithelial Regeneration

“…For example, the expression of miR-223 was significantly enhanced in the livers of high-fat diet-fed mice and overexpressed miR-223 can decrease the level of p-AKT (Zhang et al, 2020b). In experimental colitis and Kawasaki disease, overexpression of miR-223 can decrease the levels of p-STAT3 (Wang et al, 2019;Zhang et al, 2021). Furthermore, our study found that an miR-223-5p antagomir could restore the reduce the expression of p-AKT and p-STAT3 in diabetic corneas.…”

Immunohistochemical study of adhesion molecules in irritable bowel syndrome: A comparison to inflammatory bowel diseases

“…Furthermore, the pathological process underlying IBD involves the dysregulated synthesis of pro-inflammatory cytokines. [ 35 ] Thus, it would be interesting to estimate expression of inflammatory mediators that promote leukocyte/endothelial cell adhesion such as TNF-alpha, IL-1, or IL-6 which correlates with neoplasia and autoimmune disorders[ 36 37 38 ] or signaling pathways such as nuclear factor-κB, which can be activated by TNF-alpha and IL-1beta in IBS patients. [ 39 ] Finally, expression of other adhesion molecules, namely, Syndecan-1, E-cadherin/β-catenin, and proteins related with neoangiogenesis which are known for their role in colon tumorigenesis[ 40 ] could be a field for further investigation in IBS and IBD pathogenesis.…”

miRNAs Can Affect Intestinal Epithelial Barrier in Inflammatory Bowel Disease

“…In contrast, Zhang et al. (2021) observed that miR-223 agomir resulted in Bcl-2 and Bcl-xl downregulation and colonic inflammation remission in DSS-induced mice ( 81 ). Interestingly, miR-223 has been reported to be pro-inflammatory by Wang et al.…”