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Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF-b expression in the lungs of female BALB/c mice
Citation
Foong, RE and Shaw, NC and Berry, LJ and Hart, PH and Gorman, S and Zosky, GR, Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF-b expression in the lungs of female BALB/c mice, Physiological Reports, 2, (3) Article e00276. ISSN 2051-817X (2014) [Refereed Article]
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Copyright Statement
Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0) http://creativecommons.org/licenses/by/3.0/
DOI: doi:10.1002/phy2.276
Abstract
Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D-deficient or -replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five-micron sections from formalin-fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)-β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D-deficient and -replete fetal mice for quantification of ASM density and relative gene expression of TGF-β signaling pathway molecules. Eight-week-old adult vitamin D-deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D-deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D-deficient male and female mice had reduced TGF-β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF-β1 and TGF-β receptor I was downregulated in vitamin D-deficient female fetal mice. Decreased expression of TGF-β1 and TGF-β receptor I during early lung development in vitamin D-deficient mice may contribute to airway remodeling and AHR in vitamin D-deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | airway hyperresponsiveness, airway smooth muscle, lung structure, mouse model, vitamin D |
| 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: | Zosky, GR (Professor Graeme Zosky) |
| ID Code: | 95847 |
| Year Published: | 2014 |
| Deposited By: | Medicine |
| Deposited On: | 2014-10-09 |
| Last Modified: | 2017-11-02 |
| Downloads: | 382 View Download Statistics |
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