Role of circulating fibroblast growth factor-2 in lipopolysaccharide-induced acute kidney injury in mice

Pediatr Nephrol. 2012 Mar;27(3):469-83. doi: 10.1007/s00467-011-2001-z. Epub 2011 Sep 30.

Abstract

Fibroblast growth factor-2 (FGF-2) is an angiogenic growth factor involved in renal growth and regeneration. Previous studies in rodents revealed that single intrarenal injections of FGF-2 improved the outcome of acute kidney injury (AKI). Septic children usually show elevated plasma levels of FGF-2, and are at risk of developing AKI. However, the role of circulating FGF-2 in the pathogenesis of AKI is not well understood. We have developed a mouse model to determine how FGF-2 released into the circulation modulates the outcome of AKI induced by lipopolysaccharide (LPS). Young FVB/N mice were infected with adenoviruses carrying a secreted form of human FGF-2 or control LacZ vectors. Subsequently, when the circulating levels of FGF-2 were similar to those seen in septic children, mice were injected with a non-lethal dose of LPS or control buffer. All mice injected with LPS developed hypotension and AKI, from which they recovered after 5 days. FGF-2 did not improve the outcome of AKI, and induced more significant renal proliferative and apoptotic changes during the recovery phase. These findings suggest that circulating FGF-2 may not necessarily prevent the development or improve the outcome of AKI. Moreover, the renal accumulation of FGF-2 might cause further renal damage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / analysis
  • Acute Kidney Injury / blood
  • Acute Kidney Injury / etiology*
  • Acute Kidney Injury / physiopathology
  • Acute-Phase Proteins / urine
  • Adenoviridae / genetics
  • Animals
  • Apoptosis / drug effects
  • Blood Urea Nitrogen
  • Fibroblast Growth Factor 2 / blood
  • Fibroblast Growth Factor 2 / physiology*
  • Kidney / drug effects
  • Kidney / pathology
  • Lipocalin-2
  • Lipocalins / urine
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • Oncogene Proteins / urine
  • Proliferating Cell Nuclear Antigen / analysis
  • Systole / drug effects

Substances

  • ACTA2 protein, human
  • Actins
  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • Lipopolysaccharides
  • Oncogene Proteins
  • Proliferating Cell Nuclear Antigen
  • Fibroblast Growth Factor 2
  • Lcn2 protein, mouse