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

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 HUVECs-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 SD rats. Further analysis indicated that miR-106b-5p was upregulated in AGEs-sEVs and importantly, in exudate derived sEVs from patients with diabetic foot ulcer. Consequently, sEVs-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of ERK1/2, resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGE-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expres...

Source: Clinical Science - April 14, 2019 Category: Biomedical Science Authors: Zeng, T., Wang, X., Wang, W., Feng, Q., Lao, G., Liang, Y., Wang, C., Zhou, J., Chen, Y., Liu, J., Gao, H., Lan, B., Wu, Y., Han, Y., Liu, Y., Chen, H., Liu, L., Yang, C., Yan, L., Ren, M., Sun, K. Tags: PublishAheadOfPrint Source Type: research