The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function

Rachel Foong, Anthony Bosco, Anya Jones, Alexander Gout, Shelley Gorman, Prudence Hart, G.R. Zosky

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We have previously demonstrated increased airway smooth muscle (ASM) mass and airway hyperresponsiveness in whole-life vitamin D-deficient female mice. In this study, we aimed to uncover the molecular mechanisms contributing to altered lung structure and function. RNA was extracted from lung tissue of whole-life vitamin D-deficient and -replete female mice, and gene expression patterns were profiled by RNA sequencing. The data showed that genes involved in embryonic organ development, pattern formation, branching morphogenesis, Wingless/Int signaling, and inflammation were differentially expressed in vitamin D-deficient mice. Network analysis suggested that differentially expressed genes were connected by the hubs matrix metallopeptidase 9; NF-κ light polypeptide gene enhancer in B cells inhibitor, α; epidermal growth factor receptor; and E1A binding protein p300. Given our findings that developmental pathways may be altered, we investigated if the timing of vitamin D exposure (in utero vs. postnatal) had an impact on lung health outcomes. Gene expression was measured in in utero or postnatal vitamin D-deficient mice, as well as whole-life vitamin D-deficient and -replete mice at 8 weeks of age. Baseline lung function, airway hyperresponsiveness, and airway inflammation were measured and lungs fixed for lung structure assessment using stereological methods and quantification of ASM mass. In utero vitamin D deficiency was sufficient to increase ASM mass and baseline airway resistance and alter lung structure. There were increased neutrophils but decreased lymphocytes in bronchoalveolar lavage. Expression of inflammatory molecules S100A9 and S100A8 was mainly increased in postnatal vitamin D-deficient mice. These observations suggest that in utero vitamin D deficiency can alter lung structure and function and increase inflammation, contributing to symptoms in chronic diseases, such as asthma.
Original languageEnglish
Pages (from-to)664-675
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume53
Issue number5
Early online date31 Mar 2015
DOIs
Publication statusPublished - 1 Nov 2015

Fingerprint Dive into the research topics of 'The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function'. Together they form a unique fingerprint.

Cite this