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Clin Sci (Lond). 2019 May 2;133(9). pii: CS20190008. doi: 10.1042/CS20190008. Print 2019 May 15.

Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy.

Author information

1
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China.
2
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China skendo@163.com renmeng80@139.com.

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.

KEYWORDS:

autophagy; diabetic ulcer; endothelial cells; fibroblasts; small extracellular vesicles

PMID:
30988132
DOI:
10.1042/CS20190008

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