MiR-192-5p suppresses M1 macrophage polarization via epiregulin (EREG) downregulation in gouty arthritis. (December 2021)

• Record Type: Journal Article
• Authors: An, Lixin; Yin, Fuzai
• Is Part Of: Tissue & cell. Volume 73(2021)
• Publication Date: 2021-12
• Subjects: miR-192-5p -- Epiregulin -- M1 macrophages -- Gouty arthritis; Cytology -- Periodicals; 571.5
• DOI: 10.1016/j.tice.2021.101669
• Languages: English
• ISSNs: 0040-8166

Abstract

Graphical abstract: Highlights: MiR-192-5p ameliorates MSU-induced inflammatory response in GA. MiR-192-5p suppresses M1 macrophage activation. EREG is a target for miR-192-5p. EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization. Abstract: Gouty arthritis (GA) is a chronic inflammatory disease characterized by the deposition of monosodium urate (MSU) crystals within joints. MiR-192-5p is shown to be low-expressed in GA patients. However, the potential mechanism involving miR-192-5p in GA remains unclear. In the current study, a significant reduction in miR-192-5p and an increase in epiregulin (EREG) were observed in serum of GA patients, suggesting that miR-192-5p and EREG were involved in the pathogenic process of GA. A mouse GA model was established via 0.5 mg/20 μL MSU crystal administration. To investigate the effect of miR-192-5p on GA, mice were injected with miR-192-5p agomir or NC agomir before modeling. We found that miR-192-5p overexpression induced by miR-192-5p agomir reduced EREG expression, attenuated ankle joint swelling and synovial inflammatory cell infiltration and improved bone erosion in MSU-induced GA mice. MiR-192-5p decreased CD16/32 + (M1 marker) macrophages, but increased CD206 (M2 marker) expression in synovium of GA models. In vitro, RAW264.7 macrophages were stimulated with miR-192-5p mimic or NC mimic under IFNγ plus LPS-stimulated M1 polarization condition. MiR-192-5p reduced the release of inflammatory cytokines TNF-α and IL-1β, decreased iNOS expression, and inhibited CD16/32 expression, indicating the blockade of M1 macrophage activation. Luciferase reporter system revealed the target interaction between miR-192-5p and EREG. Further rescue experiments demonstrated that EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization manifested by elevated iNOS and CD16/32 levels. Collectively, miR-192-5p ameliorates inflammatory response in GA by inhibiting M1 macrophage activation via inhibiting EREG protein.