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

64 Scopus citations

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 (US)
Pages (from-to)127-133
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume406
Issue number1
DOIs
StatePublished - Mar 4 2011

Bibliographical note

Funding Information:
This study was supported by the NIH 1R01HL085613, 1R01HL097751, 1R01HL092842 (to IR), and DK075386-0251, R03DK089010-01 (to JS), and NIEHS Environmental Health Sciences Center Grant ES-01247 . We thank Dr. Haodong Xu for assisting us in pathology of lung phenotypes and Drs Rong Lu and Yong-Guo Zhang for helping with the VDR –/– mouse model.

Keywords

  • COPD
  • Inflammation
  • Lung
  • Metalloproteinases
  • Vitamin D
  • Vitamin D receptor

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