Cyclooxygenase-2 and hypoxia-regulated proteins are modulated by basic fibroblast growth factor in acute renal failure.
Acute renal failure (ARF) can be caused by injuries that induce tissue hypoxia, which in turn can trigger adaptive or inflammatory responses. We previously showed the participation of basic fibroblast growth factor (FGF-2) in renal repair. Based on this, the aim of this study was to analyze the effect of FGF-2 signaling pathway manipulation at hypoxia-induced protein levels, as well as in key proteins from the vasoactive systems of the kidney. We injected rat kidneys with FGF-2 recombinant protein (r-FGF) or FGF-2 receptor antisense oligonucleotide (FGFR2-ASO) after bilateral ischemia, and evaluated the presence of iNOS, EPO and HO-1, in representation of hypoxia-induced proteins, as well as COX-2, renin, kallikrein, and B2KR, in representation of the vasoactive systems of the kidney. A reduction in iNOS, HO-1, EPO, renin, kallikrein, B2KR, and in renal damage was observed in animals treated with r-FGF. The opposite effect was found with FGF-2 receptor down-regulation. In contrast, COX-2 protein levels were higher in kidneys treated with r-FGF and lower in those that received FGFR2-ASO, as compared to saline treated kidneys. These results suggest that the protective role of FGF-2 in the pathogenesis of ARF induced by I/R is a complex process, through which a differential regulation of metabolic pathways takes place.
Laboratory of Integrative and Molecular Physiology, Universidad de los Andes, Santiago, Chile. svillanueva@uandes.cl
Sandra
S
Villanueva
Pía
P
Escobar
Ioram
I
Jacubovsky
Carlos
C
Irarrázabal
Juan E
JE
Carreño
José M
JM
Erpel
Carlos
C
Céspedes
Alexis A
AA
González
Carlos P
CP
Vio
Victoria
V
Velarde
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007610:Kallikreins / Q000032:analysis; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000032:analysis; D015427:Reperfusion Injury / Q000503:physiopathology*
D043782:Receptor, Bradykinin B2; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D007610:Kallikreins