南方医科大学学报
南方醫科大學學報
남방의과대학학보
JOURNAL OF SOUTHERN MEDICAL UNIVERSITY
2015年
1期
29-33
,共5页
颜建云%周芹%于汇民%侯梦琳%陆立鹤
顏建雲%週芹%于彙民%侯夢琳%陸立鶴
안건운%주근%우회민%후몽림%륙립학
血管钙化%WNT%高糖%β-catenin%血管平滑肌细胞
血管鈣化%WNT%高糖%β-catenin%血管平滑肌細胞
혈관개화%WNT%고당%β-catenin%혈관평활기세포
vascular calcification%WNT%high glucose%β-catenin%vascular smooth muscle cells
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。
目的：探討高糖導緻血管鈣化機製是否與WNT信號通路有關。方法採用體外血管鈣化模型，高糖誘導血管平滑肌細胞鈣化，檢測WNT信號分子和骨相關蛋白Cbfa1，Osx，OCN，BMP2的錶達以及細胞鈣化程度。觀察WNT信號抑製劑Dkk1對高糖誘導的血管平滑肌細胞鈣化和Cbfa1，Osx，OCN，BMP2錶達的影響。結果高糖能上調血管平滑肌細胞WNT信號通路分子包括Wnt3a，Wnt7a，Fzd4，Wisp1 mRNA的錶達（1.86±0.15,1.68±0.13,2.10±0.17,2.30±0.20, P<0.05），促進WNT信號通路關鍵分子β-catenin的燐痠化（2.70±0.22, P<0.05），激活WNT信號通路。使用WNT信號抑製劑Dkk1能減輕血管平滑肌細胞鈣化，下調骨相關蛋白Cbfa1，Osx，OCN，BMP2 mRNA的錶達[（51±9）%，（58±11）%，（56±10）%，（62±10）%，P<0.01）]。結論 WNT信號通路參與瞭高糖誘導的血管平滑肌細胞鈣化。
목적：탐토고당도치혈관개화궤제시부여WNT신호통로유관。방법채용체외혈관개화모형，고당유도혈관평활기세포개화，검측WNT신호분자화골상관단백Cbfa1，Osx，OCN，BMP2적표체이급세포개화정도。관찰WNT신호억제제Dkk1대고당유도적혈관평활기세포개화화Cbfa1，Osx，OCN，BMP2표체적영향。결과고당능상조혈관평활기세포WNT신호통로분자포괄Wnt3a，Wnt7a，Fzd4，Wisp1 mRNA적표체（1.86±0.15,1.68±0.13,2.10±0.17,2.30±0.20, P<0.05），촉진WNT신호통로관건분자β-catenin적린산화（2.70±0.22, P<0.05），격활WNT신호통로。사용WNT신호억제제Dkk1능감경혈관평활기세포개화，하조골상관단백Cbfa1，Osx，OCN，BMP2 mRNA적표체[（51±9）%，（58±11）%，（56±10）%，（62±10）%，P<0.01）]。결론 WNT신호통로삼여료고당유도적혈관평활기세포개화。
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 ofβ-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.
