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

American Journal of Physiology. Lung Cellular and Molecular Physiology
Lu LiuManxiang Li

Abstract

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 S1PR2/3/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 S1PR2 antagonist JTE013, S1PR3 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 S1PR2/3 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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Citations

Jul 13, 2019·American Journal of Respiratory Cell and Molecular Biology·Jennifer L Ingram
Apr 18, 2019·Cell Communication and Signaling : CCS·Yumei LiYang Jin
Jun 17, 2020·Journal of Cellular and Molecular Medicine·Zhenan DengYuanxiong Cheng
Dec 6, 2019·Frontiers in Endocrinology·Alyson L EssexAndrea Bonetto
Apr 29, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Qin Yang, Wei Shi
Jul 21, 2021·Molecular Aspects of Medicine·Shengjie XuJoseph Jude

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Methods Mentioned

BETA
bronchoalveolar
lavage
transfection
ELISA
protein assay
nuclear translocation

Software Mentioned

Image
Pro Plus
SPSS
Quantity One

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