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

• Published in: Pediatric nephrology (Berlin, West) West), 2012-03, Vol.27 (3), p.469-483
• Main Authors: Mattison, Parnell C., Soler-García, Ángel A., Das, Jharna R., Jerebtsova, Marina, Perazzo, Sofia, Tang, Pingtao, Ray, Patricio E.
• Format: Article
• Language: English
• Subjects: Actins - analysis; Acute Kidney Injury - blood; Acute Kidney Injury - etiology; Acute Kidney Injury - physiopathology; Acute-Phase Proteins - urine; Adenoviridae - genetics; Adenoviruses; Animals; Apoptosis; Apoptosis - drug effects; Blood pressure; Blood Urea Nitrogen; Computer software industry; Fibroblast Growth Factor 2 - blood; Fibroblast Growth Factor 2 - physiology; Fibroblast growth factors; Fibroblasts; Gram-negative bacteria; Growth factors; Hostages; Intensive care; Kidney - drug effects; Kidney - pathology; Kidneys; Lipocalin-2; Lipocalins - urine; Lipopolysaccharides - toxicity; Male; Medicine; Medicine & Public Health; Mice; Mitogens; Nephrology; Oncogene Proteins - urine; Original Article; Pathogenesis; Pediatrics; Proliferating Cell Nuclear Antigen - analysis; Systole - drug effects; Tumor necrosis factor-TNF; Urology
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-011-2001-z

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.