PMID- 31204163 OWN - NLM STAT- MEDLINE DCOM- 20200403 LR - 20200403 IS - 1578-1267 (Electronic) IS - 0301-0546 (Linking) VI - 47 IP - 6 DP - 2019 Nov-Dec TI - Budesonide up-regulates vitamin D receptor expression in human bronchial fibroblasts and enhances the inhibitory effect of calcitriol on airway remodeling. PG - 585-590 LID - S0301-0546(19)30052-7 [pii] LID - 10.1016/j.aller.2019.05.001 [doi] AB - INTRODUCTION AND OBJECTIVES: Transforming growth factor beta1 (TGFbeta1) and dysregulated microRNA-21 (miR-21) expression is associated with TGFbeta/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 TGFbeta/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 TGFbeta1 for 48h. Quantitative real-time PCR was used to determine the expression of miR-21. Western blot was used to determine airway remodeling-related proteins, TGFbeta/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-related proteins. Both budesonide and calcitriol up-regulated the low expression of VDR induced by TGFbeta1 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. CI - Copyright (c) 2019. Published by Elsevier Espana, S.L.U. FAU - Xu, Yaqin AU - Xu Y AD - Department of Pediatrics, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China. FAU - Qian, Jun AU - Qian J AD - Department of Pediatrics, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China. FAU - Yu, Zhiwei AU - Yu Z AD - Department of Pediatrics, Wuxi Children's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China. Electronic address: yu98204@aliyun.com. LA - eng PT - Journal Article DEP - 20190614 PL - Singapore TA - Allergol Immunopathol (Madr) JT - Allergologia et immunopathologia JID - 0370073 RN - 0 (Anti-Inflammatory Agents) RN - 0 (MIRN21 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Receptors, Calcitriol) RN - 0 (SMAD7 protein, human) RN - 0 (Smad Proteins) RN - 0 (Smad7 Protein) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) RN - 51333-22-3 (Budesonide) RN - FXC9231JVH (Calcitriol) SB - IM MH - Airway Remodeling/drug effects MH - Anti-Inflammatory Agents/*pharmacology MH - Asthma/drug therapy/*immunology MH - Bronchi/*pathology MH - Budesonide/*pharmacology MH - Calcitriol/*pharmacology MH - Cells, Cultured MH - Drug Synergism MH - Fibroblasts/*physiology MH - Gene Expression Regulation/drug effects MH - Humans MH - MicroRNAs/genetics MH - Receptors, Calcitriol/*metabolism MH - Signal Transduction MH - Smad Proteins/metabolism MH - Smad7 Protein/genetics/metabolism MH - Transforming Growth Factor beta1/metabolism OTO - NOTNLM OT - Airway remodeling OT - Budesonide OT - Calcitriol EDAT- 2019/06/18 06:00 MHDA- 2020/04/04 06:00 CRDT- 2019/06/18 06:00 PHST- 2018/12/26 00:00 [received] PHST- 2019/05/02 00:00 [revised] PHST- 2019/05/06 00:00 [accepted] PHST- 2019/06/18 06:00 [pubmed] PHST- 2020/04/04 06:00 [medline] PHST- 2019/06/18 06:00 [entrez] AID - S0301-0546(19)30052-7 [pii] AID - 10.1016/j.aller.2019.05.001 [doi] PST - ppublish SO - Allergol Immunopathol (Madr). 2019 Nov-Dec;47(6):585-590. doi: 10.1016/j.aller.2019.05.001. Epub 2019 Jun 14.