Oncotarget

Research Papers: Pathology:

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

Hesam Movassagh, Nazanin Tatari, Lianyu Shan, Latifa Koussih, Duaa Alsubait, Mahdi Khattabi, Naresh S. Redhu, Michael Roth, Michael Tamm, Jamila Chakir and Abdelilah S. Gounni _

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Oncotarget. 2016; 7:80238-80251. https://doi.org/10.18632/oncotarget.12884

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Abstract

Hesam Movassagh1, Nazanin Tatari1, Lianyu Shan1, Latifa Koussih1,2, Duaa Alsubait1, Mahdi Khattabi1, Naresh S. Redhu1,3, Michael Roth4, Michael Tamm4, Jamila Chakir5 and Abdelilah S. Gounni1

1 Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

2 Université de Saint-Boniface, Winnipeg, Manitoba, Canada

3 Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, MA, USA

4 Department of Biomedicine, Pneumology & Pulmonary Cell Research, University Hospital Basel and University of Basel, Basel, Switzerland

5 Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie du Quebec, Universite´ Laval, Quebec City, Canada

Correspondence to:

Abdelilah S. Gounni, email:

Keywords: airway remodeling, asthma, neuropilin 1, platelet-derived growth factor, semaphorin 3A, Pathology Section

Received: June 19, 2016 Accepted: October 06, 2016 Published: October 25, 2016

Abstract

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-3β 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.


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