Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification.
Bei GuoSu-Kang ShanFeng XuXiao LinFu-Xing-Zi LiYi WangQiu-Shuang XuMing-Hui ZhengLi-Min LeiChang-Chun LiZhi-Ang ZhouMuhammad Hasnain Ehsan UllahFeng WuXiao-Bo LiaoLing-Qing YuanPublished in: Journal of nanobiotechnology (2022)
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.
Keyphrases
- vascular smooth muscle cells
- angiotensin ii
- chronic kidney disease
- mouse model
- endothelial cells
- pulmonary arterial hypertension
- induced apoptosis
- mesenchymal stem cells
- epithelial mesenchymal transition
- cell cycle arrest
- cell death
- transforming growth factor
- high glucose
- social media
- bone marrow
- endoplasmic reticulum stress
- oxidative stress
- pulmonary hypertension
- newly diagnosed
- cell proliferation