下调和上调
基因敲除
细胞生物学
BMPR2型
化学
1-磷酸鞘氨醇
小干扰RNA
细胞生长
基因沉默
癌症研究
鞘氨醇
生物
转染
受体
骨形态发生蛋白
生物化学
细胞凋亡
基因
作者
Wenhua Shi,Qingting Wang,Jian Wang,Xin Yan,Wei Feng,Qianqian Zhang,Cui Zhai,Limin Chai,Shaojun Li,Xinming Xie,Manxiang Li
摘要
Abstract The aims of the present study were to examine the molecular mechanisms underlying sphingosine‐1‐phosphate (S1P)–induced rat pulmonary artery smooth muscle cells (PASMCs) proliferation/migration and to determine the effect of yes‐associated protein (YAP) activation on S1P‐induced PASMCs proliferation/migration and its potential mechanisms. S1P induced YAP dephosphorylation and nuclear translocation, upregulated microRNA‐130a/b (miR‐130a/b) expression, reduced bone morphogenetic protein receptor 2 (BMPR2), and inhibitor of DNA binding 1(Id1) expression, and promoted PASMCs proliferation and migration. Pretreatment of cells with Rho‐associated protein kinase (ROCK) inhibitor Y27632 suppressed S1P‐induced YAP activation, miR‐130a/b upregulation, BMPR2/Id1 downregulation, and PASMCs proliferation/migration. Knockdown of YAP using small interfering RNA also suppressed S1P‐induced alterations of miR‐130a/b, BMPR2, Id1, and PASMCs behavior. In addition, luciferase reporter assay indicated that miR‐130a/b directly regulated BMPR2 expression in PASMCs. Inhibition of miR‐130a/b functions by anti‐miRNA oligonucleotides attenuated S1P‐induced BMPR2/Id1 downregulation and the proliferation and migration of PASMCs. Taken together, our study indicates that S1P induces activation of YAP through ROCK signaling and subsequently increases miR‐130a/b expression, which, in turn, downregulates BMPR2 and Id1 leading to PASMCs proliferation and migration.
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