高糖激活WNT信号通路促进血管平滑肌细胞钙化  

High glucose promotes vascular smooth muscle cell calcification by activating WNT signaling pathway

作　　者：颜建云[1] 周芹[2] 于汇民[3] 侯梦琳 陆立鹤[4] 

机构地区：[1]南方医科大学基础医学院组织胚胎学教研室,广东广州510515 [2]中山大学附属第一医院麻醉科,广东广州510080 [3]广东省人民医院心内科//广东省医学科学院广东省心血管病研究所,广东广州510080 [4]中山大学中山医学院病理生理学教研室,广东广州510080

出　　处：《南方医科大学学报》2015年第1期29-33,共5页Journal of Southern Medical University

基　　金：国家自然科学基金(81000124;81470488);中山大学高校基本科研业务费专项资金(11ykpy8);教育部留学回国人员科研启动基金资助项目~~

摘　　要：目的探讨高糖导致血管钙化机制是否与WNT信号通路有关。方法采用体外血管钙化模型,高糖诱导血管平滑肌细胞钙化,检测WNT信号分子和骨相关蛋白Cbfa1,Osx,OCN,BMP2的表达以及细胞钙化程度。观察WNT信号抑制剂Dkk1对高糖诱导的血管平滑肌细胞钙化和Cbfa1,Osx,OCN,BMP2表达的影响。结果高糖能上调血管平滑肌细胞WNT信号通路分子包括Wnt3a,Wnt7a,Fzd4,Wisp1 m RNA的表达(1.86±0.15,1.68±0.13,2.10±0.17,2.30±0.20,P<0.05),促进WNT信号通路关键分子β-catenin的磷酸化(2.70±0.22,P<0.05),激活WNT信号通路。使用WNT信号抑制剂Dkk1能减轻血管平滑肌细胞钙化,下调骨相关蛋白Cbfa1,Osx,OCN,BMP2 m RNA的表达[(51±9)%,(58±11)%,(56±10)%,(62±10)%,P<0.01)]。结论 WNT信号通路参与了高糖诱导的血管平滑肌细胞钙化。Objective To investigate whether high glucose- induced vascular calcification is associated with WNT signaling pathway. Methods An in vitro model of human vascular smooth muscle cell（VSMC） calcification was induced by exposure of the cells to high glucose. The expressions of WNT signal molecules and bone-related proteins including Cbfa1, Osx, OCN and BMP2 were analyzed with q RT-PCR, and the cell calcification was assessed by alizarin red staining. The effect of Dkk1, a WNT signaling inhibitor, on high glucose- induced cell calcification was tested with alizarin red staining and calcium content analysis. Results High glucose activated WNT signaling pathway in human VSMCs by up-regulating the expressions of WNT signal molecules including Wnt3 a, Wnt7 a, Fzd4 and Wisp1 m RNA by 1.86, 1.68, 2.1, and 2.3 folds, respectively, and by promoting the phosphorylation of β-catenin（2.70±0.22, P〈0.05）, a key mediator of WNT signaling pathway. Inhibition of WNT signaling pathway by Dkk1 attenuated high glucose-induced VSMC calcification and down-regulated the expression of bonerelated proteins Cbfa1, Osx, OCN, and BMP2 by（51 ± 9）%,（58 ± 11）%,（56 ± 10）%, and（62 ± 10）%（P〈0.01）. Conclusion WNT signaling pathway is involved in high glucose-induced VSMC calcification.

关 键 词：血管钙化 WNT 高糖 β-catenin 血管平滑肌细胞 

分 类 号：R587.2[医药卫生—内分泌]