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Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

Citation

Foong, RE and Bosco, A and Troy, NM and Gorman, S and Hart, PH and Kicic, A and Zosky, GR, Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease, American Journal of Physiology, 311, (3) pp. 653-663. ISSN 1040-0605 (2016) [Refereed Article]

Copyright Statement

Copyright 2016 the American Physiological Society

DOI: doi:10.1152/ajplung.00026.2016

Abstract

Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response and we have previously shown that airway remodelling and airway hyperresponsiveness (AHR) is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM induced increase in ASM mass and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of MID1 and ADM were differentially regulated such that they promoted inflammation, while and HILDPA which is associated with ASM remodelling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

Item Details

Item Type:Refereed Article
Keywords:vitamin D, house dust mite, asthma, genetics, airway remodeling, airway hyperresponsiveness, mouse model, RNASeq
Research Division:Medical and Health Sciences
Research Group:Cardiorespiratory Medicine and Haematology
Research Field:Respiratory Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Respiratory System and Diseases (incl. Asthma)
Author:Zosky, GR (Associate Professor Graeme Zosky)
ID Code:111013
Year Published:2016
Funding Support:National Health and Medical Research Council (1042235)
Web of Science® Times Cited:5
Deposited By:Medicine (Discipline)
Deposited On:2016-08-25
Last Modified:2018-03-07
Downloads:0

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