CONICET | Buscador de Institutos y Recursos Humanos

Introduction: In the Argentina, hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in children. The objective of our study was to analyze the tubular early response to the effect of Shiga toxin type 2 (Stx2) and the evolution to chronicity, in two experimental models in rats of SUH. Methods: Adult Sprague-Dawley rats (150-200 g) were divided in four goups for be injected by intraperitoneal route. Group 1 was injected with lethal dose (3 mL / 200 g bw) of culture supernatant of recombinant E. coli expressing Stx21. Group 2 were injected with sublethal dose (0.25 mL / 200 gbw). Groups 3 and 4 (controls 1 and 2) were injected with 3 and 0.25 mL of culture supernatant of recombinant E. coli not expressingStx2, respectively. Groups 1 and 3 were sacrificed at 48 hs and groups 2 and 4 at 1 week and 3 months post inoculation. Functional, histological, immunohistochemical, and molecular studies were performed in all groups. Results: Group 1 showed an increase in the expression of transforming growth factor beta-1 (TGF-β1) in tubularcells, which lost epithelial markers such as e-cadherin and β-catenin at 48 hs indicating an immunophenotipic change2. Moreover, we detected the novo expression of a myofibroblasts marker (Fsp-1) in renal cells indicating a development of epithelium-to-mesenchymal transition (EMT) in cortex. Group 2 showed an increase of TGF-β1 expression in the cortex at 1 week with similar histological changes observed at 48 hs. At 3 months rats presented a focal segmental glomeruloesclerosis with the presence of corticomedullary fibrotic tracts (Figure below). The increase of TGF-β1 was observed in cortex and medulla but EMT were only observed in the inner medulla. Conclusion: We have determined that the early tubular response to the effects of lethal doses of Stx2 is the development of EMT in renal cortex. On the other hands, sublethal doses of Stx2 in rats that survived to HUS showed an EMT in inner medulla with focal segmental glomeruloesclerosis and corticomedullary fibrosis. Our results suggest a different tubular response under the effect of Stx2 in dose and time dependent manner that could be related with the evolution to chronicity. 1 Zotta E, Lago N, Ochoa F, Repetto HA, Ibarra C. Development of an experimental hemolytic uremic syndrome in rats. PediatrNephrol. 23(4):559-67. 2008 2 Ochoa F, Lago, NR, Gerhardt E, Ibarra C, Zotta E. Characterization of Stx2 tubular response in a rat experimental model of hemolytic uremic syndrome (HUS). Am J Nephrol. 20;32 (4):340-346 2010

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