Role of human rhinovirus in triggering human airway epithelial-mesenchymal transition

Respiratory Research

Research

David Proud¹  Danielle M. Minor² 

[1] Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;Department of Physiology & Pharmacology, HRIC 4AC60, University of Calgary Cumming School of Medicine, 3280 Hospital Drive NW, T2N 4Z6, Calgary, Alberta, Canada;Department of Physiology & Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;University of Calgary, Faculty of Medicine, HRIC 4C50-54, 3280 Hospital Drive N.W., T2N 4Z6, Calgary, AB, Canada;

关键词: Human rhinovirus;    Epithelial-mesenchymal transition;    Transforming growth factor-β1;    E-cadherin;    Fibronectin;    MAP kinases;    SLUG;   

DOI  :  10.1186/s12931-017-0595-9

 received in 2017-04-12, accepted in 2017-05-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundStructural changes in the airways, collectively referred to as airway remodeling, are a characteristic feature of asthma, and are now known to begin in early life. Human rhinovirus (HRV)-induced wheezing illnesses during early life are a potential inciting stimulus for remodeling. Increased deposition of matrix proteins causes thickening of the lamina reticularis, which is a well-recognized component of airway remodeling. Increased matrix protein deposition is believed to be due to the presence of increased numbers of activated mesenchymal cells (fibroblasts/myofibroblasts) in the subepithelial region of asthmatic airways. The origin of these increased mesenchymal cells is not clear, but one potential contributor is the process of epithelial-mesenchymal transition (EMT). We hypothesized that HRV infection may help to induce EMT.MethodsWe used the BEAS-2B human bronchial epithelial cells line, which uniformly expresses the major group HRV receptor, to examine the effects of stimulation with HRV alone, transforming growth factor-β1 (TGF-β1), alone, and the combination, on induction of changes consistent with EMT. Western blotting was used to examine expression of epithelial and mesenchymal phenotypic marker proteins and selected signaling molecules. Cell morphology was also examined.ResultsIn this study, we show that two different strains of HRV, which use two different cellular receptors, are each capable of triggering phenotypic changes consistent with EMT. Moreover, both HRV serotypes synergistically induced changes consistent with EMT when used in the presence of TGF-β1. Morphological changes were also most pronounced with the combination of HRV and TGF-β1. Viral replication was not essential for phenotypic changes. The synergistic interactions between HRV and TGF-β1 were mediated, at least in part, via activation of mitogen activated protein kinase pathways, and via induction of the transcription factor SLUG.ConclusionsThese data support a role for HRV in the induction of EMT, which may contribute to matrix protein deposition and thickening of the lamina reticularis in airways of patients with asthma.

【 授权许可】

CC BY   
© The Author(s). 2017