β-catenin-Msx2/Runx2信号在慢性肾衰竭高磷血症诱导血管钙化中的机制

项目名称： β-catenin-Msx2/Runx2信号在慢性肾衰竭高磷血症诱导血管钙化中的机制

项目编号： No.81200542

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 戎殳

作者单位： 上海交通大学

项目金额： 25万元

中文摘要： 血管钙化(VC)是慢性肾衰竭(CRF)心血管并发症和死亡重要因素,高磷血症是引起VC的关键,常规透析不能控制高磷,因此研究CRF高磷致VC机制对控制VC、降低死亡率至关重要。结合文献和前期研究结果,我们提出BMP2-β-catenin-Msx2/Runx2信号可能是CRF高磷诱导血管平滑肌细胞表型转换,最终致VC关键机制。拟首先在体外模拟高磷状态,观察高磷和/或BMP-2作用不同时间点β-catenin,Msx2和Runx2表达及成骨标志物Sox9和Osx等表达;再采用shRNA方法抑制β-catenin表达,抑制血管平滑肌细胞向成骨表型转换,观察高磷是否促进表型转换和VC发生;进一步采用CRF动物模型,验证高磷状态下β-catenin/Msx2和β-catenin/Runx2及成骨标志物表达,VC发生,以及下调β-catenin表达后VC减轻情况。本课题将为CRF VC寻找潜在治疗靶点。

中文关键词： β-catenin-Msx2/Runx2信号；慢性肾衰竭；高磷血症；血管钙化；

英文摘要： Vascular calcification caused by chronic kidney diseases is an important reason for the cardiovascular complications and mortality in patients with chronic renal failure. Hyperphosphatemia plays and important role in the development of vascular calcification. However, conventional dialysis can not alleviate hyperphosphatemia. Therefore, the understanding of the hyperphosphatemia-induced vascular calcification in chronic renal failure is critical to control the vascular calcification and improve the quality of life. We hypothesize that the BMP2-β-catenin-Msx2/Runx2 signaling pathway might play important roles in the phenotype transition of smooth muscle cells in patients with hyperphosphatemia caused by chronic kidney diseases. Vascular smooth muscle cells will be treated with high concentrations of phosphate and/or BMP-2 and the expression of β-catenin, Msx2, Runx2, Sox9 and Osx at various time points will be determined. The phenotype transition from vascular smooth muscle cells to osteoblasts will be inhibited by knockdown of β-catenin by shRNA to understand the mechanisms of high concentration of phosphate in the vascular calcification. Using an animal model of chronic renal failure, the expression of β-catenin/Msx2, β-catenin/Runx2, and osteogenesis markers under hyperphosphatemia will be determined. In addit

英文关键词： β-catenin-Msx2/Runx2 signal；chronic renal failure；hyperphosphatemia；vascular calcification；