自噬
伤口愈合
脐静脉
细胞生物学
人脐静脉内皮细胞
细胞外
药理学
体内
细胞内
生物
成纤维细胞
体外
免疫学
生物化学
细胞凋亡
生物技术
作者
Tianyu Zeng,Xiaoyi Wang,Wei Wang,Qiling Feng,Guojuan Lao,Ying Liang,Chuan Wang,Jing Zhou,Yuying Chen,Jing Liu,Haiqi Gao,Biyun Lan,Yongwei Wu,Yuting Han,Yanyan Liu,Haishan Chen,Liyi Liu,Chuan Yang,Yan Li,Meng Ren,Kan Sun
出处
期刊:Clinical Science
[Portland Press]
日期:2019-05-01
卷期号:133 (9)
被引量:29
摘要
Abstract Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and in vivo. We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague–Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.
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