Activation of yes‐associated protein mediates sphingosine‐1‐phosphate–induced proliferation and migration of pulmonary artery smooth muscle cells and its potential mechanisms. Issue 6 (7th December 2020)

• Record Type: Journal Article
• Authors: Shi, Wenhua; Wang, Qingting; Wang, Jian; Yan, Xin; Feng, Wei; Zhang, Qianqian; Zhai, Cui; Chai, Limin; Li, Shaojun; Xie, Xinming; Li, Manxiang
• Is Part Of: Journal of cellular physiology. Volume 236:Issue 6(2021)
• Page Start: 4694
• Page End: 4708
• Publication Date: 2020-12-07
• Subjects: pulmonary artery hypertension -- pulmonary artery smooth muscle cells -- S1P -- YAP; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.30193
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : S1P induces dephosphorylation and nuclear localization of YAP through ROCK signaling and subsequently increases miR‐130a and miR‐130b expression, which further downregulates BMPR2 and Id1 leading to PASMCs proliferation and migration.