二肽基肽酶4通过ERK1／2信号通路促进人血管平滑肌细胞钙化  

Dipeptidyl peptidase-4 promotes calcification of human vascular smooth muscle cells through ERK1/2 signaling pathway

作　　者：罗未聃 王雪琴 何虎强 张雷 曾宏 刘鑫[2] 刘勇 

机构地区：[1]西南医科大学附属医院血管甲状腺外科,泸州646000 [2]泸州市人民医院神经内科

出　　处：《中华内分泌代谢杂志》2017年第4期335-340,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金项目（81270358）

摘　　要：目的探讨二肽基肽酶4（DPP4）在人血管平滑肌细胞（HVSMC）中的钙化作用及其机制。方法通过茜素红观察DPP-4对人血管平滑肌细胞（HVSMC）钙化的影响，并以Western印迹法检测细胞外信号调节激酶（ERK）1／2通路是否涉及DPP4诱导HVSMC相关钙化蛋白的表达。结果茜素红染色结果显示，DPP4组钙化结节较阴性对照组明显增多，与阳性对照组相当；且DPP4剂量和时间依赖性地促进钙化相关蛋白骨保护素（OPG）、骨桥蛋白（OPN）、Runt相关转录因子2（RUNX2）和骨形态发生蛋白2（BMP2）的表达。DPP4干预15rain明显刺激ERK1／2的磷酸化（P〈0．05），ERK1／2抑制剂可明显降低DPP4刺激的相关钙化蛋白表达（P〈0．05）。结论DPP4可能是通过ERK1／2信号通路促进HVSMC的钙化。Objective To further investigate direct effects of dipeptidyl peptidase-4 （DPP4） on calcification and to identify responsible signaling pathways in human vascular smooth muscle cells （ HVSMC ）. Methods The effect of DPP-4 on calcification of HVSMC was observed by alizarin red, and Western blot was used to detect whether DPP4 induced calcification-related protein expressions through extraeellular signal-regulated kinases 1/2 （ ERK1/2 ） pathway. Results The Alizarin red staining results showed that calcified nodules in DPP4 group were significantly increased as compared with control group, similar to calcification group. The protein expressions of osteoprotegerin （OPG）, osteopontin （OPN）, Runt-related transcription factor 2 （RUNX2）, and bone morphogenetic protein 2 （BMP2） were stimulated by DPP4 in a concentration- and time-dependent manner. The phosphorylation level of ERK1/2 was significantly increased after DPP4 incubation for 15 rain （ P〈0.05 ）. PD98059, an ERK1/2 inhibitor, significantly lowered DPP4-stimulated expressions of calcification-related proteins （ P 〈 0.05 ）. Conclusion DPP4 may promote the calcification of HVSMC through ERK1/2 signaling pathways.

关 键 词：二肽基肽酶4 血管平滑肌细胞 钙化 细胞外信号调节激酶1/2信号通路 

分 类 号：R54[医药卫生—心血管疾病]