Chevigny Mylène, Guérin-Montpetit Karine, Vargas Amandine, Lefebvre-Lavoie Josiane, Lavoie Jean-Pierre
Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada.
Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Quebec, Canada
Am J Physiol Lung Cell Mol Physiol. 2015 Jul 1;309(1):L37-45. doi: 10.1152/ajplung.00050.2015. Epub 2015 May 15.
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.
心肌细胞增生和肥大导致哮喘患者气道平滑肌（ASM）质量增加。血清反应因子（SRF）是一种转录因子，可在体外调节血管和肠道平滑肌中的心肌细胞分化。当SRF与磷酸化（p）Elk-1结合时，它会促进ASM增殖，同时与心肌素（MYOCD）结合，导致这些组织中收缩元件的表达。因此，本研究的目的是表征SRF、pElk-1和MYOCD在马的一种自发性哮喘样疾病——气喘病的中央和外周气道ASM细胞中的表达，并与对照组进行比较。研究了6匹患有气喘病的马和5匹年龄匹配、饲养在相同环境中的对照马。使用免疫组织化学和免疫荧光技术，评估了在疾病缓解期以及自然抗原暴露1天和30天后获得的外周气道和支气管内活检组织中SRF、pElk-1和MYOCD的核蛋白表达。气喘病马在疾病加重期间，外周气道中SRF的核表达（P = 0.03，缓解期与30天相比）和MYOCD的核表达（P = 0.05，对照组与气喘病马30天时相比）增加，而对照马中央气道中MYOCD的核表达（P = 0.04，缓解期与30天相比）降低。在任何一种组织中，均未观察到pElk-1蛋白表达的变化。总之，SRF及其辅因子MYOCD可能导致马哮喘气道中观察到的外周ASM肥大，而中央气道的重塑更为稳定或涉及不同的转录因子。
