Small：外泌体为促进糖尿病患者伤口愈合提供新途径
糖尿病足溃疡是糖尿病的典型并发症，在糖尿病患者中发病率高达4％。其发病诱因复杂多样，通常难以愈合且复发率高。已有研究发现，从某些细胞类型中分离得到的外泌体能够促进糖尿病伤口的愈合。然而，II型糖尿病（type 2 diabetes mellitus，T2DM）患者的循环外泌体对伤口愈合的影响仍不清楚。
近日，来自华中科技大学同济医学院附属协和医院的刘国辉、米博斌等合作研究了糖尿病患者外泌体特定miRNA在糖尿病足治疗中的潜在作用，相关研究结果发表在Small杂志上。该研究鉴定了II型糖尿病患者的循环外泌体miRNA，观察到外泌体miR-20b-5p显著上调，且该miRNA能够通过调节Wnt9b/β-catenin信号传导抑制人脐静脉内皮细胞的血管生成，将miR-20b-5p或糖尿病外泌体处理伤口部位则会减缓伤口愈合和血管生成。在糖尿病小鼠模型中，研究人员发现敲除miR-20b-5p可以显著增强伤口愈合并促进伤口血管生成，提示miR-20b-5p在T2DM患者的外泌体中高度富集并且可以转移到血管内皮细胞中，靶向Wnt9b信号传导来调节细胞功能和血管生成，为改善糖尿病相关的伤口愈合不良提供新策略。
Circulating Exosomal miR-20b-5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes-Associated Impaired Wound Healing.
At present, developing therapeutic strategies to improve wound healing in individuals with diabetes remains challenging. Exosomes represent a promising nanomaterial from which microRNAs (miRNAs) can be isolated. These miRNAs have the potential to exert therapeutic effects, and thus, determining the potential therapeutic contributions of specific miRNAs circulating in exosomes is of great importance. In the present study, circulating exosomal miRNAs are identified in diabetic patients and assessed for their roles in the context of diabetic wound healing. A significant upregulation of miR-20b-5p is observed in exosomes isolated from patients with type 2 diabetes mellitus (T2DM), and this miRNA is able to suppress human umbilical vein endothelial cell angiogenesis via regulation of Wnt9b/β-catenin signaling. It is found that the application of either miR-20b-5p or diabetic exosomes to wound sites is sufficient to slow wound healing and angiogenesis. In diabetic mice, it is found that knocking out miR-20b-5p significantly enhances wound healing and promotes wound angiogenesis. Together, these findings thus provide strong evidence that miR-20b-5p is highly enriched in exosomes from patients with T2DM and can be transferred to cells of the vascular endothelium, where it targets Wnt9b signaling to negatively regulate cell functionality and angiogenesis.