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

Movassagh, H. and Tatari, N. and Shan, L. and Koussih, L. and Alsubait, D. and Khattabi, M. and Redhu, N. S. and Roth, M. and Tamm, M. and Chakir, J. and Gounni, A. S.. (2016) Human airway smooth muscle cell proliferation from asthmatics is negatively regulated by semaphorin3A. Oncotarget, 7 (49). pp. 80238-80251.

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Official URL: https://edoc.unibas.ch/62429/

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Airway smooth muscle (ASM) hyperplasia is a key feature of airway remodeling in development of lung diseases such as asthma. Anomalous proliferation of ASM cells directly contributes to ASM hyperplasia. However, the molecular mechanisms controlling ASM cell proliferation are not completely understood. Semaphorins are versatile regulators of various cellular processes including cell growth and proliferation. The role of semaphorins in ASM cell proliferation has remained to be addressed. Here, we report that semaphorin 3A (Sema3A) receptor, neuropilin 1 (Nrp1), is expressed on human ASM cells (HASMC) isolated from healthy and asthmatic donors and treatment of these cells with exogenous Sema3A inhibits growth factor-induced proliferation. Sema3A inhibitory effect on HASMC proliferation is associated with decreased tyrosine phosphorylation of PDGFR, downregulation of Rac1 activation, STAT3 and GSK-3beta phosphorylation. Bronchial sections from severe asthmatics displayed immunoreactivity of Nrp1, suggestive of functional contribution of Sema3A-Nrp1 axis in airway remodeling. Together, our data suggest Sema3A-Nrp1 signaling as a novel regulatory pathway of ASM hyperplasia.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Pulmonary Cell Research (Roth/Tamm)
UniBasel Contributors:Roth-Chiarello, Michael and Tamm, Michael
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:12 Feb 2019 17:51
Deposited On:07 Jan 2019 19:26

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