Differential resolution of inflammation and recovery after renal ischemia-reperfusion injury in Brown Norway compared with Sprague Dawley rats.
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.
Sáenz-Morales
David
D
Department of Pathology, Hospital Ramón y Cajal, 28034, Madrid, Spain.
Conde
Elisa
E
Blanco-Sánchez
Ignacio
I
Ponte
Belen
B
Aguado-Fraile
Elia
E
de Las Casas
Gonzalo
G
García-Martos
Maria
M
Alegre
Laura
L
Escribese
Maria M
MM
Molina
Ana
A
Santiuste
Carmen
C
Liaño
Fernando
F
García-Bermejo
Maria-Laura
ML
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D018932:Chemokine CCL2; D018836:Inflammation Mediators; D039041:Integrin alpha4beta1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D016753:Interleukin-10