Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs
Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs
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DOI：
10.1080/21688370.2018.1540904
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发表时间：
2018-01-01
期刊：
影响因子：
3.1
通讯作者：
Sun, Jun
中科院分区：
文献类型：
--
作者：
Chen, Honglei;Lu, Rong;Sun, Jun
维生素D缺乏与肺部的各种炎症性疾病有关，包括肺炎、哮喘和慢性阻塞性肺病。然而，维生素D和维生素D受体减少肺部疾病炎症的机制仍然知之甚少。在这项研究中，我们研究了维生素D受体缺陷（VDR-/-）小鼠肺中紧密连接和粘附连接的表达和细胞特异性分布。我们的结果表明，在VDR-/-小鼠的肺中，claudin-2、claudin-4和claudin-12的mRNA和蛋白水平显著降低。其他紧密连接和粘附连接蛋白，如ZO-1，闭合蛋白，claudin-10，β-连环蛋白和VE-钙粘蛋白，在VDR-/-和野生型小鼠的肺中的表达显示出显着差异。这些结果提示，VDR缺失引起的慢性肺炎后紧密连接和粘附连接分子，尤其是claudin-2、claudin-4、claudin-10、claudin-12和claudin-18的表达改变，可增加肺通透性，因此，VDR可能在维持肺屏障完整性方面发挥重要作用。进一步的研究应该确认维生素D/VDR是否有益于预防或治疗肺部疾病。
Vitamin D deficiency has been linked to various inflammatory diseases in lungs, including pneumonia, asthma and chronic obstructive pulmonary disease. However, the mechanisms by which vitamin D and vitamin D receptor reduce inflammation in lung diseases remain poorly understood. In this study, we investigated the expression and cell-specific distribution of tight and adherens junctions in the lungs of vitamin D receptor-deficient (VDR-/-) mice. Our results demonstrated that mRNA and protein levels of claudin-2, claudin-4 and claudin-12 were significantly decreased in the lungs of VDR-/- mice. Other tight and adherens junction proteins, such as ZO-1, occludin, claudin-10, beta-catenin, and VE-cadherin, showed significant differences in expression in the lungs of VDR-/- and wild-type mice. These data suggest that altered expression of tight and adherens junction molecules, especially of claudin-2, -4, -10, -12, and -18, after chronic pneumonia caused by VDR deletion could increase lung permeability.Therefore, VDR may play an important role in maintaining pulmonary barrier integrity. Further studies should confirm whether vitamin D/VDR is beneficial for the prevention or treatment of lung diseases.