Abstract
Background and Objective While calcitriol can inhibit airway remodeling in asthmatic mice, the mechanism remains unclear. The purpose of this study was to explore the mechanism of action of calcitriol on airway remodeling in asthma and its interaction with budesonide. Methods A mouse model of asthma was established by allergic sensitization and challenge with ovalbumin. The mice were treated with budesonide, calcitriol, or budesonide plus calcitriol. The expression of airway remodeling-related proteins, transforming growth factor β (TGFβ) signaling pathway-related proteins, the glucocorticoid receptor, and vitamin D receptor (VDR) was determined by immunohistochemical staining and Western blot analysis. Quantitative real-time PCR was used to determine the expression of microRNA-21 (miR-21) in the lung tissue of mice. Results Monotherapy with budesonide or calcitriol inhibited the high expression of collagen type I protein and upregulated the low expression of Smad7 in asthmatic mice. There was a synergistic interaction between budesonide and calcitriol in combined treatment. The expression of miR-21 in the combined treatment group was significantly lower than that in the calcitriol treatment group. VDR expression in the combined treatment group was significantly higher than that of the calcitriol treatment group. Conclusion Budesonide and calcitriol have a synergistic effect on airway remodeling in asthmatic mice.
Highlights
Bronchial asthma is a heterogeneous disease with complex pathogenesis characterized by chronic airway inflammation and airway hyperresponsiveness
transforming growth factor β (TGFβ) plays an important role in the pathogenesis of airway remodeling in bronchial asthma [1]. e TGFβ/Smad signaling pathway is important for the biological functioning of TGFβ [2]. e imbalanced miR-21 expression is related to fibrosis and the TGFβ/Smad signaling pathway [3]
Glucocorticoid therapy cannot reduce the high expression of TGFβ in asthmatic patients, suggesting that glucocorticoid therapy alone cannot inhibit the factors involved in airway remodeling [4]
Summary
Bronchial asthma is a heterogeneous disease with complex pathogenesis characterized by chronic airway inflammation and airway hyperresponsiveness. E monotherapy with calcitriol or budesonide can inhibit airway remodeling in asthma [7, 8], but whether a combination of both exhibits a synergistic or additive effect remains unclear. In this in vivo study, we established a model of asthma in BALB/c mice by ovalbumin (Ova) sensitization and challenge and applied calcitriol, budesonide, or a combination of both to investigate the effect of calcitriol on airway remodeling in asthma, and its interaction with budesonide. While calcitriol can inhibit airway remodeling in asthmatic mice, the mechanism remains unclear. E expression of airway remodeling-related proteins, transforming growth factor β (TGFβ) signaling pathway-related proteins, the glucocorticoid receptor, and vitamin D receptor (VDR) was determined by immunohistochemical staining and Western blot analysis. Budesonide and calcitriol have a synergistic effect on airway remodeling in asthmatic mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
