AGEs刺激HUVECs来源小细胞外囊泡中miR-126-5p在糖尿病血管钙化中的保护作用
Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
Guo Bei, Shan Su-Kang, Xu Feng, Lin Xiao, Li Fu-Xing-zi, Wang Yi, Xu Qiu-Shuang, Zheng Ming-Hui, Lei Li-Min, Li Chang-Chun, Zhou Zhi-Ang, Ullah Muhammad Hasnain Ehsan, Wu Feng, Liao Xiao-Bo, Yuan Lin
Journal：JOURNAL OF NANOBIOTECHNOLOGY
IF：9.43
DOI：10.1186/s12951-022-01529-z
PMID：35842695
Published：2022-07-16
research field：血管生物学毒理学生物材料科学细胞生物学生物医学工程呼吸生物学组织工程
Abstract
The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo.Graphical Abstract
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