Circulating Exosomal miR-20b-5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes-Associated Impaired Wound Healing
Circulating Exosomal miR-20b-5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes-Associated Impaired Wound Healing
复制标题
循环外泌体 miR-20b-5p 抑制可恢复 Wnt9b 信号传导并逆转糖尿病相关的伤口愈合受损
DOI：
10.1002/smll.201904044
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发表时间：
2019-12-23
期刊：
影响因子：
13.3
通讯作者：
Liu, Guohui
中科院分区：
文献类型：
--
作者：
Xiong, Yuan;Chen, Lang;Liu, Guohui
目前，开发治疗策略以改善糖尿病患者的伤口愈合仍然具有挑战性。外切体是一种很有前途的纳米材料，可以从其中分离出microRNAs。这些miRNAs具有发挥治疗作用的潜力，因此，确定外切体中循环的特定miRNAs的潜在治疗作用具有重要意义。在目前的研究中，在糖尿病患者中发现了循环的外体miRNAs，并评估了它们在糖尿病伤口愈合中的作用。从2型糖尿病(T2 DM)患者分离的外切体中观察到miR-20b-5p的显著上调，这种miRNA能够通过调节Wnt9b/β-catenin信号来抑制人脐静脉内皮细胞的血管生成。研究发现，无论是将miR-20b-5p或糖尿病外切体应用于伤口部位，都足以减缓伤口愈合和血管生成。在糖尿病小鼠中，发现敲除miR-20b-5p显著促进伤口愈合和促进伤口血管生成。综上所述，这些发现提供了强有力的证据，表明miR-20b-5p在T2 DM患者的外切体中高度丰富，并可以转移到血管内皮细胞，在血管内皮细胞中，它靶向Wnt9b信号，负向调节细胞功能和血管生成。
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/beta-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.