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


Chen, L and Foong, R and Bennett, Ellen and Zosky, GR, In utero vitamin D deficiency alters the expression of MMPs in foetal lung, Respirology, 27-29 March, 2015, Gold Coast, Australia, pp. 140. ISSN 1323-7799 (2015) [Conference Extract]

PDF (Respirology (2015) 20 (Suppl. 2), 62–158)
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DOI: doi:10.1111/resp.12495


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.

Item Details

Item Type:Conference Extract
Keywords:Vitamin D deficiency; MMP8
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Respiratory diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Chen, L (Dr Ling Chen)
UTAS Author:Bennett, Ellen (Dr Ellen Bennett)
UTAS Author:Zosky, GR (Professor Graeme Zosky)
ID Code:100409
Year Published:2015
Deposited By:Medicine
Deposited On:2015-05-14
Last Modified:2016-03-21
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