H2型松弛素促进人血管平滑肌细胞迁移的作用及机制

目的：探讨H2型松弛素（Relaxin‐2）对血管平滑肌细胞（VSMCs）迁移的作用及分子机制。方法采用划痕实验和Transwell实验检测Relaxin‐2对VSMCs的迁移作用；采用蛋白质印迹法检测其对细胞信号蛋白丝氨酸苏氨酸蛋白激酶（Akt）、细胞外信号调节激酶（ERK）、核因子‐κB（NF‐κB） p65的影响。结果 Relaxin‐2可剂量依赖性促进VSMCs的迁移，应用NF‐κB抑制剂BAY 11‐7082可阻断Relaxin‐2诱导的基质金属蛋白酶‐9（MMP‐9）和基质金属蛋白酶‐2（MMP‐2）的表达，磷脂酰肌醇3激酶（PI3K）抑制剂LY294002和ERK抑制剂 U0126预处理可以降低Relaxin‐2引起的NF‐κB p65的激活。结论 Relaxin‐2可能通过活化PI3K／Akt和ERK信号通路激活NF‐κB p65，进而促进MMP‐9和MMP‐2的表达，从而诱导VSMCs迁移效应。

Role of Relaxin-2 in the migration of human vascular smooth muscle cells and its underlying mechanisms

Objective To investigate the effect and the associated mechanism of Relaxin‐2 in the migration of human vascular smooth muscle cells (VSMCs) .Methods The migration of VSMCs in responsing to Relaxin‐2 was evaluated by using wound heal‐ing assay and transwell assay ,and the cell signaling proteins ,including Akt ,ERK and NF‐κB p65 ,in responsing to Relaxin‐2 were measured by using Western blotting assay .Results Relaxin‐2 can promote the migration of VSMCs in a dose‐dependent manner , NF‐κB inhibitor BAY11‐7082 can block the expression of MMP‐9 and MMP‐2 induced by Relaxin‐2 ,pretreatment with PI3K inhibi‐tor LY294002 and ERK inhibitor U0126 can reduce the activation of NF‐κB p65 induced by Relaxin‐2 .Conclusion NF‐κB p65 could be activated by the activation of PI3K/Akt and ERK signaling pathway induced by Relaxin‐2 ,thereby promoting the expression of MMP‐9 and MMP‐2 ,and inducing VSMCs migration effect .