Vitamin D alleviates lipopolysaccharide‑induced acute lung injury via regulation of the renin‑angiotensin system

Mol Med Rep. 2017 Nov;16(5):7432-7438. doi: 10.3892/mmr.2017.7546. Epub 2017 Sep 20.

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. ALI and ARDS result are associated with high mortality in patients. At present, no effective treatments for ALI and ARDS exist. It is established that vitamin D exhibits anti‑inflammatory effects, however, the specific effect of vitamin D on ALI remains largely unknown. The aim of the present study was to investigate whether, and by which mechanism, vitamin D alleviates lipopolysaccharide (LPS)‑induced ALI. The results demonstrated that a vitamin D agonist, calcitriol, exhibited a beneficial effect on LPS‑induced ALI in rats; calcitriol pretreatment significantly improved LPS‑induced lung permeability, as determined using Evans blue dye. Results from reverse transcription‑quantitative polymerase chain reaction, western blotting and ELISA analysis demonstrated that calcitriol also modulated the expression of members of the renin‑angiotensin system (RAS), including angiotensin (Ang) I‑converting enzymes (ACE and ACE2), renin and Ang II, which indicates that calcitriol may exert protective effects on LPS‑induced lung injury, at least partially, by regulating the balance between the expression of members of the RAS. The results of the present study may provide novel targets for the future treatment of ALI.

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / metabolism
  • Angiotensin II / analysis*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Lipopolysaccharides / toxicity*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Microvessels / cytology
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Renin / analysis*
  • Renin-Angiotensin System / drug effects*
  • Vitamin D / pharmacology*

Substances

  • Lipopolysaccharides
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Angiotensin II
  • Vitamin D
  • Peptidyl-Dipeptidase A
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • Renin