CKAP4通过YAP核转移促进Gli1阳性间充质干细胞的成骨分化在慢性肾脏病血管钙化中的机制研究

血管钙化(VC)和骨/矿物质紊乱，被描述为慢性肾病(CKD)矿物质骨紊乱(MBD)，VC是导致CKD心血管并发症和死亡的重要因素, 目前针对VC治疗效果不理想，VC发病机制是肾脏病领域重要研究方向。查阅文献发现，Gli1+间充质干细胞（MSC）在其中起重要作用。我们前期研究发现CKD伴随CKAP4血清水平增加，推测CKAP4通过YAP核转移促进Gli1+MSC成骨分化，促进血管钙化。本研究将从临床观察CKD患者血清CKAP4与VC的相关性;在动物水平构建Gli1CreERt2;tdtomoto小鼠CKD模型,在细胞水平分离获得CKD小鼠原代Glil+细胞,构建CKAP4过表达载体，利用遗传命运追踪、离体荧光反射成像、流式细胞仪和siRNA沉默基因等技术明确CKAP4促进Gli1+MSC成骨分化效应及胞内分子机制。该研究对于揭示CKD VC机制有重要意义。

Vascular calcification (VC) and bone/mineral disorders, described as chronic kidney disease (CKD) mineral bone disorder (MBD), VC is an important factor leading to cardiovascular complications and death of CKD, currently not effective for VC treatment, The pathogenesis of VC is an important research direction in the field of kidney disease. The literature found that Gli1+ mesenchymal stem cells (MSC) play an important role in it. Previous studies have found that CKD is accompanied by an increase in serum levels of CKAP4. We hypothesize that CKAP4 promotes osteogenic differentiation of Gli1+MSCs through YAP nuclear transfer and promotes vascular calcification. This study will clinically observe the correlation between serum CKAP4 and VC in CKD patients; construct Gli1CreERt2 at the animal level; CKD model of tdtomoto mice, obtain CKD mouse primary Glil+ cells at the cellular level, construct CKAP4 overexpression vector, and use genetic fate Techniques such as tracking, in vitro fluorescence reflex imaging, flow cytometry and siRNA silencing genes clarify that CKAP4 promotes osteogenic differentiation and intracellular molecular mechanisms of Gli1+MSC. This study is important for revealing the CKD VC mechanism.