title: 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 VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.
authors.affiliation: Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Box 850, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Isaac K
authors.initials: IK
authors.lastname: Sundar
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Hwang
authors.forename: Shaoping
authors.initials: S
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
mesh_terms: D000818:Animals; D004646:Emphysema / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017353:Gene Deletion; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D018167:Receptors, Calcitriol; D020782:Matrix Metalloproteinases