Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

Isaac K Sundar, Jae-woong Hwang, Shaoping Wu, Jun Sun, Irfan Rahman

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)127-33
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume406
Issue number1
DOIs
Publication statusPublished - Mar 2011

Keywords

  • vitamin D receptor
  • Vitamin D
  • INFLAMMATION
  • Metalloproteinase
  • LUNG
  • COPD

Fingerprint Dive into the research topics of 'Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation'. Together they form a unique fingerprint.

Cite this