title: Role of circulating fibroblast growth factor-2 in lipopolysaccharide-induced acute kidney injury in mice.
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.
authors.affiliation: Division of Nephrology, Center for Molecular Physiology Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Parnell C
authors.initials: PC
authors.lastname: Mattison
authors.forename: Angel A
authors.initials: AA
authors.lastname: Soler-García
authors.forename: Jharna R
authors.initials: JR
authors.lastname: Das
authors.forename: Marina
authors.initials: M
authors.lastname: Jerebtsova
authors.forename: Sofia
authors.initials: S
authors.lastname: Perazzo
authors.forename: Pingtao
authors.initials: P
authors.lastname: Tang
authors.forename: Patricio E
authors.initials: PE
authors.lastname: Ray
mesh_terms: D000199:Actins / Q000032:analysis; D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D000209:Acute-Phase Proteins / Q000652:urine; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000502:physiology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D015513:Oncogene Proteins / Q000652:urine; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013599:Systole / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2; C071332:Lcn2 protein, mouse