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

Sphingosine-1-phosphate induces airway smooth muscle cells proliferation, migration and contraction by modulating Hippo signaling effector YAP. Am J Physiol Lung Cell Mol Physiol. 2018 Jul 12;: Authors: Liu L, Zhai C, Pan Y, Zhu Y, Shi W, Wang J, Yan X, Su X, Song Y, Gao L, Li M 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 cells (ASMCs) 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) de-phosphorylation and nuclear localization via S1PR2/3/Rho-associated protein kinase (ROCK) pathway, and this in turn increased forkhead box M1 (FOXM1) and cyclin D1 expression leading to ASMCs proliferation, migration and contraction. Pre-treatment of cells with S1PR2 antagonist JTE013 or S1PR3 antagonist CAY10444 or ROCK inhibitor Y27632 blocked S1P-induced alterations of YAP, FOXM1, cyclin D1 and ASMCs proliferation, migration and contraction. In addition, prior silencing YAP or FOXM1 with siRNA reversed the effect of S1P on ASMCs functions. Taken together, our study indicates that S1P stimulates ASMCs 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. ...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research