内质网应激下PRRX1通过IRE1α-XBP1s抑制血管平滑肌细胞钙化的机制研究

陆 冰清1, 王 姿懿2, 袁 媛3, 杨 萍*3
1、南通大学附属南通市妇幼保健院
2、江苏大学医学院
3、上海中医药大学附属龙华医院

摘要


目的：探讨内质网应激（ERS）下配对相关同源框1（PRRX1）通过肌醇需要的酶1α（IRE1α）-剪切型X-box结合蛋白1（XBP1s）通路对血管平滑肌细胞（VSMC）钙化的调控及作用机制。方法：将VSMC分为四组：空白对照组、钙化组、钙化+空载体组、钙化+过表达PRRX1组。建立VSMC钙化模型，采用免疫荧光、茜素红染色分析各组细胞的钙化情况；采用蛋白质印迹、RT-qPCR分析钙化相关指标（Runx2、BMP2）以及ERS标志物（Grp78、IRE1α、XBP1s）的蛋白及mRNA表达差异。结果：与空白对照组相比，钙化组的PRRX1蛋白表达降低，Runx2、BMP2蛋白及mRNA的表达明显升高；过表达PRRX1后，与钙化+空载体组比较，PRRX1的表达显著升高，钙沉积面积减少，钙化指标以及内质网应激指标的蛋白及mRNA表达均下降，以上差异均有统计学意义（P<0.05）。结论：PRRX1对VSMC钙化具有抑制作用，其机制为在ERS下通过IRE1α-XBP1s通路减少VSMC的成骨细胞转化。

关键词


血管钙化；内质网应激；PRRX1

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参考


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