title: Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses.
abstract: Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors.
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Mylène
authors.initials: M
authors.lastname: Chevigny
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Karine
authors.initials: K
authors.lastname: Guérin-Montpetit
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Amandine
authors.initials: A
authors.lastname: Vargas
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
authors.forename: Josiane
authors.initials: J
authors.lastname: Lefebvre-Lavoie
authors.affiliation: Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada jean-pierre.lavoie@umontreal.ca.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lavoie
mesh_terms: D056151:Airway Remodeling / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006734:Horse Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006736:Horses; D006965:Hyperplasia / Q000473:pathology; D006984:Hypertrophy / Q000473:pathology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism; D011485:Protein Binding; D026362:Serum Response Factor / Q000096:biosynthesis*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000378:metabolism; D050807:ets-Domain Protein Elk-1 / Q000096:biosynthesis*; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D050807:ets-Domain Protein Elk-1; D000099251:Myocardin
keywords: Elk-1; airway smooth muscle; asthmatic airways; myocardin; serum-response factor