Budesonide up-regulates vitamin D receptor expression in human bronchial fibroblasts and enhances the inhibitory effect of calcitriol on airway remodeling
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Keywords
Airway remodeling, Budesonide, Calcitriol
Abstract
Introduction and objectives: Transforming growth factor 1 (TGF1) and dysregulated microRNA-21 (miR-21) expression is associated with TGF/Smad signaling pathway activation and fibrosis. While calcitriol has been shown to improve airway remodeling in asthmatic mice, its mechanism remains unknown. In this study, the effect of calcitriol on the TGF/Smad signaling pathway and miR-21 expression in human bronchial fibroblasts was investigated to explore the mechanism of action of calcitriol and the inhaled glucocorticoid, budesonide, in airway remodeling.
Materials and methods: Human bronchial fibroblasts were pretreated with budesonide, calcitriol, or budesonide plus calcitriol, and stimulated with TGF1 for 48 h. Quantitative real-time PCR was used to determine the expression of miR-21. Western blot was used to determine airway remodeling-related proteins, TGF/Smad signaling pathway-related proteins, glucocorticoid receptor, and vitamin D receptor (VDR) expression.
Results: Both budesonide and calcitriol down-regulated miR-21 expression in human bronchial fibroblasts, up-regulated Smad7 expression, and inhibited the expression of airway remodeling elated proteins. Both budesonide and calcitriol up-regulated the low expression of VDR induced by TGF1 in human bronchial fibroblasts. The expression of VDR in the combined treatment group (budesonide plus calcitriol) was significantly higher than that in the calcitriol treatment group. The expression of collagen type I in the combined treatment group was significantly lower than that in the calcitriol treatment group.
Conclusions: Calcitriol can up-regulate the expression of VDR in human bronchial fibroblasts and exert an anti-airway remodeling effect. Budesonide can up-regulate the expression of VDR in human bronchial fibroblasts and enhance the inhibitory effect of calcitriol on airway remodeling.
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