Vitamin D regulating TGF-β induced epithelial-mesenchymal transition

Background: Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. A critical regulator of fibrosis, transforming growth factor beta (TGF-beta), 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. Methods: Human bronchial epithelial cells (BEAS-2B) were exposed to calcitriol followed by stimulation with TGF-beta 1 or TGF-beta 2. 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. Results: TGF-beta 1 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-beta 2 elicited migratory response similar to TGF-beta 1 but induced the expression of EMT markers differently from that by TGF-beta 1. Calcitriol attenuated TGF-beta 1- and TGF-beta 2-induced cell motility. Also, calcitriol inhibited the expression of EMT markers in TGF-beta 1-treated epithelial cells with less effect on TGF-beta 2. Conclusions: These data suggest that calcitriol inhibits both migration and invasion induced by TGF-beta 1 and TGF-beta 2 in human airway epithelial cells. However, the regulatory effect of vitamin D in epithelial-mesenchymal transition was more effective to TGF-beta 1-induced changes. Thus, calcitriol could be a potential therapeutic agent in the prevention and management of subepithelial fibrosis and airway remodeling.