Abstract OBJECTIVE: To establish a mouse model of asthmatic airway remodeling and investigate the effects of 1,25-(OH)2D3 on airway structure and T cell immunoglobulin mucin protein-4 (TIM-4) expression in asthmatic mice. METHODS: Thirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)2D3 intervention groups. An asthmatic mouse model was induced using ovalbumin. Lung tissue of the mice was collected, mRNA expression of TIM-4 was evaluated by RT-PCR and airway remodeling and protein expression of TIM-4 were observed by hematoxylineosin staining and immunohistochemistry.RESULTS: Typical airway remodeling was found in the asthma group, and TIM-4 expression in this group was significantly higher than in the control group (105±9 vs 42±5; P<0.05). Compared with the asthma group, the 1,25-(OH)2D3 intervention group showed improvement in airway remodeling and a decrease in TIM-4 expression (78±6) (P<0.05). CONCLUSIONS: TIM-4 may be involved in the airway remodeling of mice. As a new type of immunoregulator, 1,25-(OH)2D3 can downregulate expression of TIM-4 in the lungs and improve airway remodeling in asthmatic mice.
［13］Bikle DD. Vitamin D regulation of immune function［J］. Vitam Horm, 2011, 86: 1-21.
［3］Miner JL.The adipocyte as an endocrine cell［J］. J Anim Sci, 2004, 82(3): 935-941.
［14］Sandhu MS, Casale TB. The role of vitamin D in asthma［J］. Ann Allergy Asthma Immunol, 2010, 105(3): 191-199.
［4］Lefebvre AM, Laville M, Vega N, Riou JP, van Gaal L, Auwerx J, et al. Depot-specific differences in adipose tissue gene expression in lean and obese subjects［J］. Diabetes, 1998, 47(1): 98-103.
［5］Hida K, Wada J, Eguchi J, Zhang H, Baba M, Seida A, et al.Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity［J］. Proc Natl Acad Sci U S A, 2005, 102(30): 10610-10615.
［15］Damera G, Fogle HW, Lim P, Goncharova EA, Zhao H, Banerjee A, et al. Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1［J］. Br J Pharmacol, 2009, 158(6): 1429-1441.
［6］Kloting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schon MR, et al. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes［J］. Biochem Biophys Res Commun, 2006, 339(1):430-436.
［7］Blüher M. Vaspin in obesity and diabetes: pathophysiological and clinical significance［J］. Endocrine, 2012, 41(2):176-182.
［8］Tan BK, Heutling D, Chen J, Farhatullah S, Adya R, Keay SD, et al. Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance［J］. Diabetes, 2008, 57(6):1501-1507.
［9］Chandler PC, Viana JB, Oswald KD, Wauford PK, Boggiano MM. Feeding response to melanocortin agonist predicts preference for and obesity from a high-fat diet［J］. Physiol Behav, 2005, 85(2): 221-230.
［16］Morris HA, Anderson PH. Autocrine and paracrine actions of vitamin D［J］. Clin Biochem Rev, 2010, 31(4): 129-138.
［17］Back O, Blomquist HK, Hernell O, Stenberg B. Does vitamin D intake during infancy promote the development of atopic allergy?［J］. Acta Derm Venereol, 2009, 89(1): 28-32.
