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Differential resolution of inflammation and recovery after renal ischemia-reperfusion injury in Brown Norway compared with Sprague Dawley rats

Saenz-Morales, David
Conde, Elisa
Blanco-Sanchez, Ignacio
Aguado-Fraile, Elia
de Las Casas, G.
Garcia-Martos, M.
Alegre, L.
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Published in Kidney International. 2010, vol. 77, no. 9, p. 781-793
Abstract To investigate mechanisms conferring susceptibility or resistance to renal ischemia, we used two rat strains known to exhibit different responses to ischemia-reperfusion. We exposed proximal tubule cells isolated from Sprague Dawley or Brown Norway rats, to a protocol of hypoxia, followed by reoxygenation in vitro. The cells isolated from both rat strains exhibited comparable responses in the disruption of intercellular adhesions and cytoskeletal damage. In vivo, after 24 h of reperfusion, both strains showed similar degrees of injury. However, after 7 days of reperfusion, renal function and tubular structure almost completely recovered and inflammation resolved, but only in Brown Norway rats. Hypoxia-inducible factor-dependent gene expression, ERK1/2, and Akt activation were different in the two strains. Inflammatory mediators MCP-1, IL-10, INF-gamma, IL-1beta, and TNF-alpha were similarly induced at 24 h in both strains but were downregulated earlier in Brown Norway rats, which correlated with shorter NFkappaB activation in the kidney. Moreover, VLA-4 expression in peripheral blood lymphocytes and VCAM-1 expression in kidney tissues were initially similar at 24 h but reached basal levels earlier in Brown Norway rats. The faster resolution of inflammation in Brown Norway rats suggests that this strain might be a useful experimental model to determine the mechanisms that promote repair of renal ischemia-reperfusion injury.
Keywords AnimalsAnoxia/genetics/metabolismChemokine CCL2/genetics/metabolismGene ExpressionInflammation/genetics/metabolismInflammation Mediators/metabolismIntegrin alpha4beta1/genetics/metabolismInterleukin-10/genetics/metabolismIschemia/genetics/*metabolismKidney/metabolism/physiopathologyKidney Diseases/genetics/metabolismKidney Function TestsKidney Tubules, Proximal/metabolism/physiopathologyMaleRatsRats, Inbred BNRats, Sprague-DawleyReperfusion Injury/genetics/*metabolism/*physiopathologySpecific Pathogen-Free OrganismsTumor Necrosis Factor-alpha/genetics/metabolismVascular Cell Adhesion Molecule-1/genetics/metabolism
PMID: 20164827
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Other version: http://www.nature.com/ki/journal/v77/n9/pdf/ki201010a.pdf
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SAENZ-MORALES, David et al. Differential resolution of inflammation and recovery after renal ischemia-reperfusion injury in Brown Norway compared with Sprague Dawley rats. In: Kidney International, 2010, vol. 77, n° 9, p. 781-793. doi: 10.1038/ki.2010.10 https://archive-ouverte.unige.ch/unige:21277

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Deposited on : 2012-05-23

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