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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)L609-L621
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number4
DOIs
StatePublished - Oct 1 2018

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Smooth Muscle Myocytes
Cell Movement
Cell Proliferation
Cyclin D1
Asthma
rho-Associated Kinases
Nuclear Proteins
Protein Kinases
Small Interfering RNA
sphingosine 1-phosphate
Lipids
Forkhead Box Protein M1

Keywords

  • Asmcs
  • Foxm1
  • S1p
  • Yap

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating hippo signaling effector yap. / Liu, Lu; Zhai, Cui; Pan, Yilin; Zhu, Yanting; Shi, Wenhua; Wang, Jian; Yan, Xin; Su, Xiaofan; Song, Yang; Gao, Li; Li, Manxiang.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 315, No. 4, 01.10.2018, p. L609-L621.

Research output: Contribution to journalArticle

Liu, Lu ; Zhai, Cui ; Pan, Yilin ; Zhu, Yanting ; Shi, Wenhua ; Wang, Jian ; Yan, Xin ; Su, Xiaofan ; Song, Yang ; Gao, Li ; Li, Manxiang. / Sphingosine-1-phosphate induces airway smooth muscle cell proliferation, migration, and contraction by modulating hippo signaling effector yap. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2018 ; Vol. 315, No. 4. pp. L609-L621.
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