title: Human airway smooth muscle cell proliferation from asthmatics is negatively regulated by semaphorin3A.
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.
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Hesam
authors: H
authors: Movassagh
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Nazanin
authors: N
authors: Tatari
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Lianyu
authors: L
authors: Shan
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.|Université de Saint-Boniface, Winnipeg, Manitoba, Canada.
authors: Latifa
authors: L
authors: Koussih
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Duaa
authors: D
authors: Alsubait
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Mahdi
authors: M
authors: Khattabi
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.|Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
authors: Naresh S
authors: NS
authors: Redhu
authors: Department of Biomedicine, Pneumology & Pulmonary Cell Research, University Hospital Basel and University of Basel, Basel, Switzerland.
authors: Michael
authors: M
authors: Roth
authors: Department of Biomedicine, Pneumology & Pulmonary Cell Research, University Hospital Basel and University of Basel, Basel, Switzerland.
authors: Michael
authors: M
authors: Tamm
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie du Quebec, Universite´ Laval, Quebec City, Canada.
authors: Jamila
authors: J
authors: Chakir
authors: Department of Immunology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Abdelilah S
authors: AS
authors: Gounni
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D005260:Female; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C107953:RAC1 protein, human; C108639:SEMA3A protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D040121:Semaphorin-3A; D039942:Neuropilin-1; D017479:Receptors, Platelet-Derived Growth Factor; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D020830:rac1 GTP-Binding Protein
keywords: Pathology Section; airway remodeling; asthma; neuropilin 1; platelet-derived growth factor; semaphorin 3A