miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis

in Journal of Molecular Endocrinology
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  • 1 Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China
  • | 2 Department of Nuclear Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, People’s Republic of China

Correspondence should be addressed to J Jiang: jjj890456@163.com

*(X Peng and F He contributed equally to this work)

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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.

 

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