MiR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis. (23rd May 2022)

• Record Type: Journal Article
• Authors: Peng, Xuefeng; He, Fang; Mao, Yanling; Lin, Yihui; Fang, Jingwen; Chen, Yangchun; Sun, Zhichun; Zhuo, Yafen; Jiang, Jianjia
• Is Part Of: Journal of molecular endocrinology. Volume 69:Number 2(2022)
• Page Start: 315
• Page End: 327
• Publication Date: 2022-05-23
• Subjects: diabetic ulcers -- wound healing -- macrophages -- M2 polarization -- microRNA-146a -- TLR4 -- NF-κB; Molecular endocrinology -- Periodicals; Endocrinology -- Periodicals; 616.407
• DOI: 10.1530/JME-21-0019
• Languages: English
• ISSNs: 0952-5041

Abstract

Abstract : We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.