Abstract
BackgroundSubepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. A critical regulator of fibrosis, transforming growth factor β (TGF-β), can induce airway remodeling in epithelial cells through induction of epithelial-mesenchymal transition (EMT). Vitamin D has immunomodulatory functions, however, its effect on controlling subepithelial fibrosis is not known.MethodsHuman bronchial epithelial cells (BEAS-2B) were exposed to calcitriol followed by stimulation with TGF-β1 or TGF-β2. The protein expression and mRNA transcripts for E-cadherin, Snail, vimentin, and N-cadherin were analyzed by Western blot and qPCR. An invasion assay and scratch wound assay were performed to identify the migratory properties of the cells following treatments.ResultsTGF-β1 decreased E-cadherin expression and increased protein expression and mRNA transcripts of Snail, vimentin, and N-cadherin together with increased cell invasion and migration. TGF-β2 elicited migratory response similar to TGF-β1 but induced the expression of EMT markers differently from that by TGF-β1. Calcitriol attenuated TGF-β1- and TGF-β2-induced cell motility. Also, calcitriol inhibited the expression of EMT markers in TGF-β1-treated epithelial cells with less effect on TGF-β2.ConclusionsThese data suggest that calcitriol inhibits both migration and invasion induced by TGF-β1 and TGF-β2 in human airway epithelial cells. However, the regulatory effect of vitamin D in epithelial-mesenchymal transition was more effective to TGF-β1-induced changes. Thus, calcitriol could be a potential therapeutic agent in the prevention and management of subepithelial fibrosis and airway remodeling.
Highlights
Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma
transforming growth factor (TGF)-β1 induces epithelial-mesenchymal transition (EMT) characteristics EMT is defined by changes in gene expression in which epithelial markers such as E-cadherin decrease while mesenchymal markers such as N-cadherin and vimentin increase
BEAS-2B cells were stimulated with increasing doses of TGF-β1 ranging from 0.1 ng/ml up 50 ng/ml
Summary
Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. A critical regulator of fibrosis, transforming growth factor β (TGF-β), can induce airway remodeling in epithelial cells through induction of epithelial-mesenchymal transition (EMT). Asthma is a chronic inflammatory disease that results in the narrowing of the airways, tightening of the chest, shortness of breath, and coughing. The hallmarks of asthma include airway obstruction, chronic wheezing, airway hyperresponsiveness, airway remodeling, inflammation, and mucus hypersecretion. While current treatments include corticosteroids, leukotriene antagonists, and long-acting β2 agonists, these therapies are not effective in preventing or reversing airway remodeling in patients suffering from chronic allergic asthma [2]. Further understanding of the mechanisms underlying airway remodeling is required to develop therapies that target the molecules involved in structural changes, including fibrosis and epithelial thickening
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