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In utero vitamin D deficiency alters the expression of MMPs in foetal lung

conference contribution
posted on 2023-05-24, 13:42 authored by Chen, L, Foong, R, Ellen Bennett, Graeme ZoskyGraeme Zosky

Aim: Vitamin D deficiency has been shown to impair lung development. Using a mouse model we have identified several genes that have altered expression in adult female lungs in response to whole-life vitamin D deficiency including nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA), epidermal growth factor receptor (EGFR), matrix metalloproteinase 8 (MMP8), MMP9, S100 calcium binding protein A8 (S100A8), and S100A9. In this study we aimed to determine whether these genes show altered expression in the developing foetal lung in response to vitamin D deficiency.

Methods: A mouse model of vitamin D deficiency was established by dietary manipulation. Pregnant vitamin D-deficient and –replete mice and their pups were euthanized at gestational day 17.5 (E17.5). Foetal lungs were collected (vitamin D-replete female n = 5, male n = 5; vitamin D-deficient female n = 6, male n = 6) for real time quantitative PCR to determine the gene expression. Fold change in gene expression was normalized to ribosomal protein L37 endogenous control gene.

Results: Both NFKBIA (p < 0.001) and EGFR (p = 0.019) gene expression were higher in the lungs of female mice than male mice but there was no effect of vitamin D deficiency. MMP8 expression was higher in female lungs than male lungs (p < 0.001) and was also down-regulated by vitamin D deficiency. There were no impact of sex or diet on the expression of MMP9, S100A8 and S100A9.

Conclusion: MMP8 is known to be important in airway remodelling which may explain our observation that in utero vitamin D deficiency increases airway smooth muscle mass in adulthood. This observation supports a role for vitamin D in airway development and may explain the association between early life vitamin D deficiency and an increased risk of asthma in childhood.

History

Publication title

Respirology

Volume

20 (Suppl. 2)

Editors

P Bardin

Pagination

140

ISSN

1323-7799

Department/School

Tasmanian School of Medicine

Publisher

Wiley-Blackwell Publishing Asia

Place of publication

Australia

Event title

Thoracic Society of Australia & New Zealand and the Australian & New Zealand Society of Respiratory Science 2015 Annual Scientific Meetings

Event Venue

Gold Coast, Australia

Date of Event (Start Date)

2015-03-27

Date of Event (End Date)

2015-03-29

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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