Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs

Abstract

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, β-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. ARTICLE HISTORY

The Role of Vitamin C, Vitamin D, and Selenium in Immune System against COVID-19

“…Vitamin D Improving the physical barriers of the body by regulating the production of proteins for tight junctions [50], adherens junctions [51], and gap junctions [52] Stimulating the production of antimicrobial peptides, such as cathelicidin and defensins [55] Modulating T helper (Th) cell responses to induce a shift from Th1 to Th2 responses [61,62,64] Preventing cytokine storms by decreasing inflammatory cytokines [67,68] and nuclear factor κB (NF-κB) activation [69] Inverse correlation between vitamin D level and viral respiratory tract infection [38][39][40] Vitamin D deficiency/insufficiency observed in patients with COVID-19 [41] Inverse correlation between COVID-19 mortality and sunlight exposure [45] or vitamin D level [43,48] Worse prognosis in COVID-19 patients with a low level of vitamin D [47,49] Selenium Preventing mutations in viral genome [71][72][73] Increasing CD4 + T cell activation, proliferation, and differentiation; inducing Th1 phenotype [74] Enhancing the function of cytotoxic effector cells by increasing the cytotoxicity of CD8 + T cells and lytic activity of natural killer (NK) cells [77] Maintaining T cell maturation and functions, including T cell-dependent antibody production [79,80] Preventing vasoconstriction and blood coagulation [87], which may increase COVID-19 mortality [81] Higher selenium level in surviving COVID-19 patients compared to deceased patients [16] Higher recovery rate from COVID-19 in patients with higher selenium levels [17] Author Contributions: Conceptualization: H.K. ; investigation, writing, and original draft preparation: M.B.…”

Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections

“…In addition, in a viral infection model, dsRNA increased the expression of the 1α-hydroxylase and synergizes with calcifediol and calcitriol sequentially to induce cathelicidin [64]. Apart from defensins (such as cathelicidin), 1α,25(OH)2D also stimulates several genes in these ACII cells with favorable effects such as stimulation of surfactant factor and tight junction genes [65]. In a mouse model, 1α,25(OH)2D attenuated LPS-induced lung injury by promoting epithelial cell proliferation, and inhibited apoptosis and epithelial mesenchymal transition, suggesting that VDR activation may have therapeutic potential for the resolution of ARDS [40].…”

Dietary micronutrients in the wake of COVID-19: an appraisal of evidence with a focus on high-risk groups and preventative healthcare

“…Deletion has the potential to increasing lung permeability and reduce pulmonary barrier integrity. 27 The activation of vitamin D in the lung has the potential to induce these antimicrobials and attenuate inflammatory cytokines in response to viruses. Higher vitamin D status is associated with decreased levels of proinflammatory cytokines and conversely low status appears to be associated with the activation of inflammatory processes, which is particularly relevant in the case of sepsis derived from lung infection.…”