Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway
Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway
复制标题
模拟生理拉伸通过整合素 α 4/α v-FAK-ERK1/2 信号通路增加人膀胱平滑肌细胞中细胞外基质蛋白的表达
DOI：
10.1007/s00345-016-1993-1
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发表时间：
2017-08-01
影响因子：
3.4
通讯作者：
Wang, Kunjie
中科院分区：
文献类型：
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作者：
Chen, Shulian;Peng, Chuandu;Wang, Kunjie
目的探讨模拟生理拉伸对细胞外基质（ECM）蛋白表达的影响，以及整合素α 4/ α v、局点黏附激酶（FAK）、细胞外调节蛋白激酶1/2 （ERK1/2）在拉伸诱导的人膀胱平滑肌细胞（HBSMCs） ECM蛋白表达中的作用。方法将HBSMCs植入硅胶膜上，在拉伸率为5%、10%和15%的情况下进行模拟生理拉伸。实时聚合酶链反应和Western blot检测HBSMCs中初代ECM蛋白的表达。FAK抑制剂和ERK1/2抑制剂（PD98059）的Western blot检测FAK和ERK1/2的特异性。用小干扰核糖核酸（siRNA）转染检测整合素α 4和整合素α v的特异性。结果在模拟生理拉伸10%和15%的情况下，ⅰ型胶原（Col1）、ⅲ型胶原（Col3）和纤维连接蛋白（Fn）的表达显著升高。与静态条件相比，10%模拟生理拉伸激活整合素α 4和α v、FAK、ERK1/2。预处理ERK1/2抑制剂、FAK抑制剂、整合素α 4 siRNA或整合素α v siRNA可降低拉伸诱导的ECM蛋白表达。FAK抑制剂降低拉伸诱导的ERK1/2活性和ECM蛋白表达。整合素α 4 siRNA或整合素α v siRNA抑制FAK的拉伸诱导活性。结论模拟生理拉伸增加了HBSMCs中ECM蛋白的表达，整合素α 4/ α v-FAK-ERK1/2信号通路部分调节了机械转导过程。
Objectives To investigate the effect of simulated physiological stretch on the expression of extracellular matrix (ECM) proteins and the role of integrin alpha 4/alpha v, focal adhesion kinase (FAK), extracellular regulated protein kinases 1/2 (ERK1/2) in the stretch-induced ECM protein expression of human bladder smooth muscle cells (HBSMCs).Methods HBSMCs were seeded onto silicone membrane and subjected to simulated physiological stretch at the range of 5, 10, and 15% elongation. Expression of primary ECM proteins in HBSMCs was analyzed by real-time polymerase chain reaction and Western blot. Specificity of the FAK and ERK1/2 was determined by Western blot with FAK inhibitor and ERK1/2 inhibitor (PD98059). Specificity of integrin alpha 4 and integrin alpha v was determined with small interfering ribonucleic acid (siRNA) transfection.Results The expression of collagen I (Col1), collagen III (Col3), and fibronectin (Fn) was increased significantly under the simulated physiological stretch of 10 and 15%. Integrin alpha 4 and alpha v, FAK, ERK1/2 were activated by 10% simulated physiological stretch compared with the static condition. Pretreatment of ERK1/2 inhibitor, FAK inhibitor, integrin alpha 4 siRNA, or integrin alpha v siRNA reduced the stretch-induced expression of ECM proteins. And FAK inhibitor decreased the stretch-induced ERK1/2 activity and ECM protein expression. Integrin alpha 4 siRNA or integrin alpha v siRNA inhibited the stretch-induced activity of FAK.Conclusion Simulated physiological stretch increases the expression of ECM proteins in HBSMCs, and integrin alpha 4/alpha v-FAK-ERK1/2 signaling pathway partly modulates the mechano-transducing process.