Vitamin D supplementation decreases the expression of TGF-β1 in rats with asthma and thereby suppressing airway remodeling

Abstract

Objective To investigate the preventive and therapeutic effects of 1, 25-(OH)2D3 on airway remodeling in asthmatic rats, and to explore the effect of 1, 25-(OH)2D3 on the expression of transforming growth factor-β1 (TGF-β1) and the related mechanism between them. Methods Seventy male Sprague Dawley (SD) rats were randomly divided into seven groups: normal control group (group A, n=10), asthmatic group (group B, n=10), dexamethasone group (group C, n=10), 1, 25-(OH)2D3 2 μg/(kg·d) group (group D, n=10), 1, 25-(OH)2D3 4 μg/(kg·d) group (group E, n=10), 1, 25-(OH)2D3 8 μg/(kg·d) group (group F, n=10), 1, 25(OH)2D3 16 μg/(kg·d) group (group G, n=10). Rats were sensitized and challenged with ovalbumin (OVA) to establish the asthmatic model in B, C, D, E, F, G group respectively. Rats in group B and group C were fed with normal saline 10 ml/(kg·d) and dexamethasone 2 mg/(kg·d) before atomization. While group D-G was 1, 25- (OH)2D3 intervention group, rats were fed with vitamin D 2, 4, 8, 16 μg/(kg·d) before atomization. The number of total and different cells of the bronchoalveolar lavage fluid (BALF) from the 7 groups was counted for analysis; The change of the thickness, the area of airway wall and the number of ASMC nucleus and pulmonary tissue changes were observed by microscope. The protein and mRNA expression of TGF-β1 in the lung tissue was measured by immunochemistry and real-time polymerase chain reaction (RT-PCR). Results ⑴ The airway remodeling and pulmonary inflammatory exudation in the B group were significantly heavier than those in the A, C and G groups (P<0.01); and the difference between groups of different doses of vitamin D [D group (minimum dose) and G group(the maximum dose) ] was statistically significant (P<0.01). ⑵ The results of TGF-β1 mRNA and protein levels in rats of each group showed that the expression level of TGF-β1 mRNA and integrated option density (IOD) value in A group were significantly lower than those in other groups (P<0.01); the expression level of TGF-β1 mRNA and IOD value in B group was higher than the other groups (P<0.01); Compared with the B group, the expression level of TGF-β1 mRNA and IOD value in G group (large dose vitamin D group) was decreased, with statistically difference. Conclusions In the rat model of asthma, 1, 25-(OH)2D3 may alleviate airway remodeling by regulating the expression of TGF- beta 1 and play its opposite biological effect in the prevention and treatment of asthma. Key words: Asthma; Rats; Transforming growth factor beta1; Vitamin D; Airway remodeling