ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1598781
This article is part of the Research TopicInnovative Immunoregulation Strategies in the Chronic Inflammation-Based DiseasesView all 5 articles
miR-223 alleviates DSS-induced colitis by prompting macrophage M2 polarization through PPAR-γ/FOXO1 signaling
Provisionally accepted
- Affiliated Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China
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Macrophage polarization represents a promising therapeutic target for inflammatory bowel disease (IBD). This study investigates the role of miRNA-223 (miR-223) in dextran sodium sulfate (DSS)-induced colitis and its regulation of macrophage polarization. Male C57BL/6 mice were assigned to four groups: Wild-type (WT) control, DSS-treated group (DSS), DSS+miR-223 agomir (DSS+A), and DSS+ miR-223 agomir negative control (DSS+NC). Colitis was induced with 2.5% DSS for 7 days; miR-223 agomir or NC was administered intraperitoneally on days 2-4. We evaluated disease activity index (DAI), colonic inflammation, and the expression of inflammatory mediators, peroxisome proliferator-activated receptor gamma (PPAR-γ) and forkhead box transcription factor O1 (FOXO1). Histopathological analysis showed that miR-223 agomir significantly attenuated DSS-induced colon damage. Proinflammatory cytokines (TNF-α, IL-1β, IL-6) increased in DSS mice, while antiinflammatory IL-10 decreasedtrends reversed by miR-223 supplementation at mRNA/protein levels. Mechanistically, DSS elevated M1 macrophage marker iNOS and FOXO1 but reduced M2 marker Arg1 and PPAR-γ. miR-223 agomir suppressed M1 polarization while enhancing M2 polarization by downregulating FOXO1 and upregulating PPAR-γ. We identify a novel dual-regulatory mechanism wherein miR-223 ameliorates colitis by shifting macrophage polarization from M1 to M2 via concurrent FOXO1 suppression and PPAR-γ activation. These findings establish a mechanistic basis for miR-223 supplementation as a novel IBD therapeutic strategy.
Keywords: MiRNA-223, DSS-induced colitis, intestinal macrophages, Macrophage polarization, Inflammatory bowel disease (IBD)
Received: 24 Mar 2025; Accepted: 09 Jul 2025.
Copyright: © 2025 Zhang, Wang, Shen, Qian, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chenyang Wang, Affiliated Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210093, Jiangsu Province, China
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