MicroRNA-30b通过调节自噬参与慢性肾脏病血管钙化的机制研究

Vascular calcification is a common complication in patients with chronic kidney disease (CKD), and is a critical factor for cardiovascular events. It has been shown that autophagy plays an important role in vascular calcification, but the role of miRNA in autophagy and vascular calcification is not clear. In our previous work, we found that miR-30b targeted Wnt5A and Beclin 1 to affect vascular smooth muscle cell (VSMC) autophagy and vascular calcification. Moreover, we found that Wnt/β-catenin-pit1 signaling pathway was involved in high-phosphorus induced calcification. Based on these results, our project aims to apply clinical samples and human VSMCs to explore the role of miR-30b-Wnt5A-Wnt/β-catenin and miR-30b-Beclin 1 signaling pathways in autophagy and vascular calcification by applying the molecular and cellular biology methods. Besides, we aim to establish a rat model of CKD to identify the possibility of intervention the aforementioned signaling pathways to reverse the vascular calcification. This project will provide novel targets and strategies for treatment of vascular calcification in CKD patients.

血管钙化是慢性肾脏病（CKD）患者常见并发症之一，是心血管事件的重要原因。研究表明，细胞自噬在血管钙化中发挥重要作用，然而miRNA在自噬和血管钙化过程中的作用及其调节机制尚不清楚。本课题组前期工作显示，CKD高磷状态下miR-30b可以靶向Wnt5A和Beclin 1，进而影响大鼠血管平滑肌细胞（VSMCs）自噬和钙化；并发现Wnt/β-catenin-pit1通路介导高磷诱导的VSMCs钙化过程。在此基础上，本项目拟采用病人样本和人VSMCs，利用分子和细胞生物学手段，验证miR-30b-Wnt5A-Wnt/β-catenin和miR-30b-Beclin 1信号通路对VSMCs自噬和血管钙化的影响；并构建CKD大鼠模型，验证干预上述信号通路对逆转血管钙化的可行性。本课题为防治慢性肾脏病血管钙化提供新的靶点和策略。

血管钙化是慢性肾脏病（CKD）患者常见并发症之一，是心血管事件的重要原因。研究表明，细胞自噬在血管钙化中发挥重要作用，然而miRNA在自噬和血管钙化过程中的作用及其调节机制尚不清楚。本课题组前期工作显示，CKD高磷状态下miR-30b可以靶向Wnt5A和Beclin 1，进而影响大鼠血管平滑肌细胞（VSMCs）自噬和钙化；并发现Wnt/β-catenin-pit1通路介导高磷诱导的VSMCs钙化过程。在此基础上，本项目采用人VSMCs，利用分子和细胞生物学手段，验证miR-30b-Wnt5A-Wnt/β-catenin和miR-30b-Beclin 1信号通路对VSMCs自噬和血管钙化的影响；并构建CKD大鼠模型，验证干预上述信号通路对逆转血管钙化的可行性。本课题为防治慢性肾脏病血管钙化提供新的靶点和策略。

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