2011
DOI: 10.1016/j.bbrc.2011.02.011
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Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that V… Show more

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Cited by 94 publications
(82 citation statements)
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“…In airway epithelial cells, VitD induces the expression of the antimicrobial peptide cathelicidin (16,17). VitD deficiency in mice causes alterations in the structure of the lung with decreased functional capacity (18), and deletion of the VDR leads to premature emphysema (19). Surprisingly, a recent paper showed that dietary VitD deficiency did not result in a frank change of the pulmonary response to lipopolysaccharide (LPS) in a mouse model (20).…”
mentioning
confidence: 99%
“…In airway epithelial cells, VitD induces the expression of the antimicrobial peptide cathelicidin (16,17). VitD deficiency in mice causes alterations in the structure of the lung with decreased functional capacity (18), and deletion of the VDR leads to premature emphysema (19). Surprisingly, a recent paper showed that dietary VitD deficiency did not result in a frank change of the pulmonary response to lipopolysaccharide (LPS) in a mouse model (20).…”
mentioning
confidence: 99%
“…The zymography was performed to determine the activity of MMPs in mouse lungs as described previously (46,47). Briefly, the lung tissue was homogenized with 50 mM Tris·HCl (pH 7.4) on ice, and lung homogenates that contained 200 g of protein were mixed with an equal volume of sample buffer [80 mmol/l Tris·HCl (pH 6.8), 4% SDS, 10% glycerol, 0.01% bromophenol blue].…”
Section: Ethics Statementmentioning
confidence: 99%
“…In combination with transcription factors and coregulatory proteins, the 1,25(OH) 2 D 3 -VDR complex promotes or suppresses the transcription of a wide range of genes (76). VDR knockout in mice results in early-onset emphysema and decline in lung function, with lymphoid aggregate formation secondary to inflammatory changes (94). More subtle mutations or polymorphisms in the VDR gene, which may affect gene promotion, RNA transcription efficacy, or protein structure, have been associated with a variety of diseases, such as such as multiple sclerosis, type I diabetes mellitus, osteoporosis, and colon, breast, and prostate cancer (49,74,97).…”
mentioning
confidence: 99%