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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

© 2016 the American Physiological Society.
Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness 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 midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid dropletassociated, which is associated with ASM remodeling, 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.
Original languageEnglish
Pages (from-to)L653-L663
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number3
DOIs
Publication statusPublished - Sep 2016

Fingerprint

Vitamin D Deficiency
Pyroglyphidae
Pneumonia
Genes
Smooth Muscle
Airway Resistance
Bronchoalveolar Lavage
Inflammation
Vitamin D
Lung
RNA
Cytokines
Adrenomedullin
Airway Remodeling
Methacholine Chloride
Bronchoalveolar Lavage Fluid
Metaplasia
Mucus
Proteins
Down-Regulation

Cite this

@article{a03056eb4087430f97d5ebe9ecfd42fb,
title = "Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease",
abstract = "{\circledC} 2016 the American Physiological Society.Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness 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 midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid dropletassociated, which is associated with ASM remodeling, 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.",
author = "Foong, {Rachel E.} and Anthony Bosco and Troy, {Niamh M.} and Shelley Gorman and Hart, {Prue H.} and Anthony Kicic and G.R. Zosky",
year = "2016",
month = "9",
doi = "10.1152/ajplung.00026.2016",
language = "English",
volume = "311",
pages = "L653--L663",
journal = "AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "3",

}

TY - JOUR

T1 - Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease

AU - Foong, Rachel E.

AU - Bosco, Anthony

AU - Troy, Niamh M.

AU - Gorman, Shelley

AU - Hart, Prue H.

AU - Kicic, Anthony

AU - Zosky, G.R.

PY - 2016/9

Y1 - 2016/9

N2 - © 2016 the American Physiological Society.Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness 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 midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid dropletassociated, which is associated with ASM remodeling, 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.

AB - © 2016 the American Physiological Society.Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness 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 midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid dropletassociated, which is associated with ASM remodeling, 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.

U2 - 10.1152/ajplung.00026.2016

DO - 10.1152/ajplung.00026.2016

M3 - Article

VL - 311

SP - L653-L663

JO - AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

JF - AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

SN - 1040-0605

IS - 3

ER -