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

2018 ◽  
Vol 315 (4) ◽  
pp. L609-L621 ◽  
Author(s):  
Lu Liu ◽  
Cui Zhai ◽  
Yilin Pan ◽  
Yanting Zhu ◽  
Wenhua Shi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Cyclin D1 ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Molecular Mechanisms ◽  
Airway Smooth Muscle Cell ◽  
Hippo Signaling ◽  
Rock Inhibitor ◽  
Sphingosine 1 Phosphate

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.

scholarly journals Novel phosphodiesterases inhibitors from the group of purine-2,6-dione derivatives as potent modulators of airway smooth muscle cell remodelling

2019 ◽  
Vol 865 ◽  
pp. 172779 ◽  
Author(s):  
Katarzyna Wójcik-Pszczoła ◽  
Grażyna Chłoń-Rzepa ◽  
Agnieszka Jankowska ◽  
Eugenie Ellen ◽  
Artur Świerczek ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Airway Smooth Muscle Cell

scholarly journals Cytokines and Growth Factors Promote Airway Smooth Muscle Cell Proliferation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
R. Stamatiou ◽  
E. Paraskeva ◽  
K. Gourgoulianis ◽  
P.-A. Molyvdas ◽  
A. Hatziefthimiou
Keyword(s):  
Smooth Muscle ◽  
Growth Factors ◽  
Smooth Muscle Cell ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Thymidine Incorporation ◽  
Cell Number ◽  
Airway Smooth Muscle Cell ◽  
Specific Cell ◽  
Dependent Manner

Chronic airway diseases, such as asthma or chronic obstructive pulmonary disease, are characterized by the presence in the airways of inflammation factors, growth factors and cytokines, which promote airway wall remodelling. The aim of this study was to investigate the effect of cytokines and growth factors on airway smooth muscle cell (ASMC) proliferation, phenotype and responsiveness. Incubation of serum starved human bronchial ASMCs with TNF-α, TGF, bFGF, and PDGF, but not IL-1β, increased methyl-[3H]thymidine incorporation and cell number, mediated by the PI3K and MAPK signalling pathways. Regarding rabbit tracheal ASMC proliferation, TNF-α, IL-1β, TGF, and PDGF increased methyl-[3H]thymidine incorporation in a PI3K- and MAPK-dependent manner. bFGF increased both methyl-[3H]thymidine incorporation and cell number. Moreover, incubation with TGF, bFGF and PDGF appears to drive human ASMCs towards a synthetic phenotype, as shown by the reduction of the percentage of cells expressing SM-α actin. In addition, the responsiveness of epithelium-denuded rabbit tracheal strips to carbachol was not significantly altered after 3-day treatment with bFGF. In conclusion, all the tested cytokines and growth factors increased ASMC proliferation to a different degree, depending on the specific cell type, with bronchial ASMCs being more prone to proliferation than tracheal ASMCs.

scholarly journals Human airway smooth muscle cell proliferation from asthmatics is negatively regulated by semaphorin3A

Oncotarget ◽  
2016 ◽  
Vol 7 (49) ◽  
pp. 80238-80251 ◽  
Author(s):  
Hesam Movassagh ◽  
Nazanin Tatari ◽  
Lianyu Shan ◽  
Latifa Koussih ◽  
Duaa Alsubait ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Airway Smooth Muscle ◽  
Muscle Cell ◽  
Airway Smooth Muscle Cell ◽  
Smooth Muscle Cell Proliferation ◽  
Human Airway Smooth Muscle ◽  
Human Airway
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