Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification

被引：26

作者：

Guo, Bei ^{[1
]}

Shan, Su-Kang ^{[1
]}

Xu, Feng ^{[1
]}

Lin, Xiao ^{[2
]}

Li, Fu-Xing-zi ^{[1
]}

Wang, Yi ^{[1
]}

Xu, Qiu-Shuang ^{[1
]}

Zheng, Ming-Hui ^{[1
]}

Lei, Li-Min ^{[1
]}

Li, Chang-Chun ^{[1
]}

Zhou, Zhi-Ang ^{[4
]}

Ullah, Muhammad Hasnain Ehsan ^{[1
]}

Wu, Feng ^{[3
]}

Liao, Xiao-Bo ^{[4
]}

Yuan, Ling-Qing ^{[1
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Natl Clin Res Ctr Metab Dis, Dept Metab & Endocrinol, Changsha 410000, Peoples R China

[2] Cent South Univ, Xiangya Hosp 2, Dept Radiol, Changsha, Hunan, Peoples R China

[3] Cent South Univ, Xiangya Hosp 2, Dept Pathol, Changsha, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Hosp 2, Dept Cardiovasc Surg, Changsha, Hunan, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2022年 / 20卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Vascular calcification; Diabetes; sEVs; miR-126-5p; Endothelial cells; GLYCATION END-PRODUCTS; EXOSOMES; CELLS; RUNX2; INDUCTION; REPAIR; KRAS;

D O I：

10.1186/s12951-022-01529-z

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页数：17

共 66 条

[1] Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription [J].