Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.
Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice.
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DOI：
10.1371/journal.pone.0149180
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Fischer KD;Hall SC;Agrawal DK
哮喘是一种与气道高反应性（AHR）、气道阻塞和气道重塑相关的慢性肺部疾病。气道重塑涉及气道上皮细胞通过上皮-间充质转化（EMT）分化为肌成纤维细胞，从而加剧上皮下纤维化的程度。EMT涉及E-钙粘蛋白的丢失，同时间充质标志物（包括波形蛋白和N-钙粘蛋白）的增加。越来越多的证据表明，维生素D具有免疫调节和抗炎特性。然而，这些影响的潜在分子机制仍不清楚。在这项研究中，我们研究了维生素D对AHR，气道炎症和EMT标记物在小鼠气道中的表达的贡献，这些小鼠用临床相关过敏原，屋尘螨，豚草和链格孢属（HRA）的组合致敏和激发。雌性Balb/c小鼠喂食维生素D充足（2000 IU/kg）或维生素D补充（10，000 IU/kg）的饲料，然后用HRA致敏。检测支气管肺泡灌洗液（BALF）中炎性细胞密度、肺组织学和免疫荧光法检测EMT标志物的表达。在HRA致敏和激发小鼠中，与维生素D不足相比，补充维生素D可降低AHR、BALF中的气道炎症和气道重塑特征。这伴随着气道中E-钙粘蛋白表达增加，波形蛋白和N-钙粘蛋白表达减少。这些结果表明，维生素D可能是一个有益的辅助治疗方案在过敏性哮喘。
Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma.