Budesonide and Calcitriol Synergistically Inhibit Airway Remodeling in Asthmatic Mice

Can Respir J. 2018 May 2:2018:5259240. doi: 10.1155/2018/5259240. eCollection 2018.

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.

MeSH terms

  • Airway Remodeling / drug effects*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy
  • Asthma / metabolism
  • Budesonide / pharmacology
  • Budesonide / therapeutic use*
  • Calcitriol / pharmacology
  • Calcitriol / therapeutic use*
  • Calcium-Regulating Hormones and Agents / pharmacology
  • Calcium-Regulating Hormones and Agents / therapeutic use*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Female
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism
  • Ovalbumin
  • Random Allocation
  • Receptors, Calcitriol / metabolism
  • Receptors, Glucocorticoid / metabolism
  • Retinoid X Receptors / metabolism
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Anti-Inflammatory Agents
  • Calcium-Regulating Hormones and Agents
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Receptors, Calcitriol
  • Receptors, Glucocorticoid
  • Retinoid X Receptors
  • Smad Proteins
  • Transforming Growth Factor beta
  • Budesonide
  • Ovalbumin
  • Calcitriol