National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
J Nanobiotechnology. 2022 Jul 16;20(1):334. doi: 10.1186/s12951-022-01529-z.
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.
糖尿病患者血管钙化的发病机制仍难以捉摸。作为一种有效的信息传递者，小细胞外囊泡 (sEVs) 携带丰富的 microRNAs (miRNAs)，调节受体细胞的生理和病理状态。在本研究中，从人脐静脉内皮细胞 (HUVECs) 中分离的 sEVs 在受到糖基化终产物 (AGEs/sEVs) 刺激后，观察到 miR-126-5p 显著上调。有趣的是，这些 sEVs 通过靶向 BMPR1B 抑制血管平滑肌细胞 (VSMCs) 的成骨分化，BMPR1B 编码 BMP 的受体，从而阻断 smad1/5/9 信号通路。此外，在 2 型糖尿病小鼠模型中，敲低 HUVECs 中的 miR-126-5p 可显著减弱 AGEs/sEVs 的抗钙化作用。总之，miR-126-5p 在 AGEs 刺激的 HUVECs 衍生的 sEVs 中高度富集，并能靶向 BMPR1B，在体外和体内负调控 VSMCs 的转分化。
