| First Author | Foong RE | Year | 2014 |
| Journal | Physiol Rep | Volume | 2 |
| Issue | 3 | Pages | e00276 |
| PubMed ID | 24760528 | Mgi Jnum | J:228475 |
| Mgi Id | MGI:5707133 | Doi | 10.1002/phy2.276 |
| Citation | Foong RE, et al. (2014) Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF-beta expression in the lungs of female BALB/c mice. Physiol Rep 2(3):e00276 |
| abstractText | 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)-beta 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-beta 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-beta levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF-beta1 and TGF-beta receptor I was downregulated in vitamin D-deficient female fetal mice. Decreased expression of TGF-beta1 and TGF-beta 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. |
