Journal
CLINICAL SCIENCE
Volume 133, Issue 9, Pages -Publisher
PORTLAND PRESS LTD
DOI: 10.1042/CS20190008
Keywords
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Categories
Funding
- National Natural Science Foundation of China [81600642, 81471034, 8137091, 81300675]
- Natural Science Foundation of Guangdong Province, China [2015A030310433, 2017A030313831]
- Sun Yat-sen University Medical 2016 Youth Teacher Research Funding Project [16ykpy27]
- Sun Yat-sen Clinical Research Cultivating Program [SYS-Q-201801]
- Major Project of the People's Livelihood Science and Technology in Guangzhou [201300000102]
- 863 Project of Young Scientist [SS2015AA020927]
- Zhujiang Star of Science and Technology Foundation in Guangzhou [2014J2200046]
- Chinese Society of Endocrinology and National Clinical Research Center for Metabolic Diseases
- State Key Clinical Specialty Construction Project (2011)
- Science and Technology Planning Project of Guangdong Province, China [2014A020212161]
- National Key R&D Program of China [2016YFC0901200]
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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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