Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP | Zendy

Lu Liu | Zendy; Cui Zhai | Zendy; Yilin Pan | Zendy; Yanting Zhu | Zendy; Wenhua Shi | Zendy; Jian Wang | Zendy; Xin Yan | Zendy; Xiaofan Su | Zendy; Yang Song | Zendy; Li Gao | Zendy; Manxiang Li | Zendy

Open Access

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating Hippo signaling effector YAP

Author(s) -

Lu Liu,

Cui Zhai,

Yilin Pan,

Yanting Zhu,

Wenhua Shi,

Jian Wang,

Xin Yan,

Xiaofan Su,

Yang Song,

Li Gao,

Manxiang Li

Publication year - 2018

Publication title -

ajp lung cellular and molecular physiology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.892

H-Index - 163

eISSN - 1522-1504

pISSN - 1040-0605

DOI - 10.1152/ajplung.00554.2017

Subject(s) - sphingosine 1 phosphate , microbiology and biotechnology , foxm1 , sphingosine kinase 1 , sphingosine , cell growth , chemistry , sphingosine kinase , rho associated protein kinase , cell migration , hippo signaling pathway , signal transduction , endocrinology , biology , medicine , receptor , cell , cell cycle , biochemistry

Sphingosine-1-phosphate (S1P), a bioactive lipid, has been shown to be elevated in the airways of individuals with asthma and modulates the airway smooth muscle cell (ASMC) functions, yet its underlying molecular mechanisms are not completely understood. The aim of the present study is to address this issue. S1P induced yes-associated protein (YAP) dephosphorylation and nuclear localization via the S1PR 2/3 /Rho-associated protein kinase (ROCK) pathway, and this in turn increased forkhead box M1 (FOXM1) and cyclin D1 expression leading to ASMC proliferation, migration, and contraction. Pretreatment of cells with S1PR 2 antagonist JTE013, S1PR 3 antagonist CAY10444, or ROCK inhibitor Y27632 blocked S1P-induced alterations of YAP, FOXM1, cyclin D1, and ASMC proliferation, migration, and contraction. In addition, prior silencing of YAP or FOXM1 with siRNA reversed the effect of S1P on ASMC functions. Taken together, our study indicates that S1P stimulates ASMC proliferation, migration, and contraction by binding to S1PR 2/3 and modulating ROCK/YAP/FOXM1 axis and suggests that targeting this pathway might have potential value in the management of asthma.

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