高糖激活WNT信号通路促进血管平滑肌细胞钙化

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 mRNA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 mRNA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。

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

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 qRT-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 Wnt3a, Wnt7a, Fzd4 and Wisp1 mRNA 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
bone-related 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.