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1 Departamento de Fisiologia, Pontificia Universidad Catolica de Chile, Santiago, RM, Chile
* To whom correspondence should be addressed. E-mail: svillanu{at}bio.puc.cl.
Ischemia induced acute renal failure (ARF) is a disorder with high morbidity and mortality. ARF is characterized by a regeneration phase yet its molecular basis is still under study. Changes in gene expression have been reported in ARF being some of these genes specific of nephrogenic processes. We tested the hypothesis that the regeneration process developed after ARF induced by ischemia, can be characterized by the re-expression of important regulatory proteins of kidney development.
The distribution pattern and levels of nephrogenic proteins in rat kidneys after ischemia were studied by immunohistochemistry and immunoblot analysis. Ischemic damage was assessed by conventional morphology, serum creatinine and the apoptotic markers TUNEL and Caspase 3. The hypoxia levels induced by ischemia were assessed by specific markers: HIF-1
and 2-Pimonidazole.
In kidneys with ARF an important initial damage was observed through PAS staining, by the induction of damage markers -SMA and ED-1 and by apoptosis induction. In agreement with diminishing of renal damage at the initial reparation phase, the expression of the mesenchymal proteins Vimentin, Ncam and the epithelial markers, Pax-2, Noggin and bFGF were observed; after, in a middle time the tubular markers BMP-7, Engrailed and Lim-1 and transcription factors Smad and p-Smad were observed. Additionally, the endothelial markers VEGF and Tie-2 were induced at the initial and middle stages of regeneration phase, respectively. The expression of these proteins was restricted in time and space. The expression of these proteins was restricted spatially and temporally.
Because all these proteins are important to generate a functional kidney, these results suggest that during the regeneration process induced by hypoxia, these nephrogenic proteins can be re-expressed in a similar fashion to that observed during development, thus restoring mature kidney function.
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