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

被引：38

作者：

Liu, Lu ^{[1
]}

Zhai, Cui ^{[1
]}

Pan, Yilin ^{[1
]}

Zhu, Yanting ^{[1
]}

Shi, Wenhua ^{[1
]}

Wang, Jian ^{[1
]}

Yan, Xin ^{[1
]}

Su, Xiaofan ^{[1
]}

Song, Yang ^{[1
]}

Gao, Li ^{[2
]}

Li, Manxiang ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, 277 Yanta West Rd, Xian 710061, Shaanxi, Peoples R China

[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY | 2018年 / 315卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ASMCs; FOXM1; S1P; YAP; SPHINGOSINE; 1-PHOSPHATE; RHO/RHO-KINASE; GROWTH-CONTROL; ORGAN SIZE; PATHWAY; ACTIVATION; RECEPTOR; PROTEIN; ASTHMA; CANCER;

D O I：

10.1152/ajplung.00554.2017

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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.

引用

页码：L609 / L621

页数：13

共 67 条

[1] Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma [J].