miR-146a 通过抑制 TLR4/NF-κB 轴促进 M2 巨噬细胞极化并加速糖尿病伤口愈合。
miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.
机构信息
Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, People's Republic of China.
Department of Nuclear Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, People's Republic of China.
出版信息
J Mol Endocrinol. 2022 May 23;69(2):315-327. doi: 10.1530/JME-21-0019.
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.
我们试图揭示 miR-146a 在糖尿病创面愈合中 M2 巨噬细胞极化作为生物标志物的临床意义。首先，我们发现糖尿病患者的巨噬细胞中 miR-146a 减少。接下来，双荧光素酶报告基因实验验证了 TLR4 是 miR-146a 的靶基因，并且受 miR-146a 负调控。此外，进行 miR-146 和/或 TLR4 的异位表达和耗尽实验后，检测到巨噬细胞的脂多糖诱导的炎症反应。结果表明，miR-146a 通过抑制 TLR4/核因子-κB（NF-κB）轴促进 M2 巨噬细胞极化，从而增强糖尿病溃疡的愈合。进一步建立糖尿病溃疡的小鼠模型，以体内研究 miR-146a 对糖尿病创面愈合的影响，结果表明 miR-146a 通过抑制 TLR4/NF-κB 轴促进糖尿病溃疡的愈合。总之，我们证明 miR-146a 通过抑制 TLR4/NF-κB 轴可以诱导 M2 巨噬细胞极化，从而增强糖尿病溃疡的愈合。
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