Endostatin expression in the murine model of ischaemia/reperfusion-induced acute renal failure

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Nephrology
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Background: Renal ischaemia-hypoxia is a leading cause of acute renal failure, a clinical condition associated with rapid loss of renal function and high rates of mortality. Renal proximal tubular cells are the most severely injured during renal ischaemia, caused by the breakdown of the extracellular matrix of the tubular basement membrane. Endostatin is the C-terminal fragment of collagen XVIII generated by proteolytic cleavage and it is well-known as being an inhibitor of angiogenesis. In vitro, endostatin inhibits endothelial cell proliferation and migration, as well as tubule formation. In vivo, it has a potent inhibitory effect on tumour growth. In this study, we analysed endostatin gene expression in C57BL/6 mouse kidneys subjected to ischaemia/reperfusion. Methods: Ischaemic renal failure was induced via 45 min of bilateral occlusion of the renal artery and vein, followed by 12 h or 24 h of reperfusion. Whole-kidney homogenate and total RNA were extracted for examination by western blot analysis and quantitative polymerase chain reaction. The immunohistological examination revealed increased endostatin expression in injured kidney, mainly in the proximal tubule and collecting ducts. Results: Endostatin/collagen XVIII mRNA and protein expression increased during ischaemia and within 12 h of reperfusion. In the western blot assay, we identified increased expression of the 30 kDa endostatin-related fragment and of matrix metalloproteinase-9. CD31 was significantly expressed during reperfusion (P < 0.05). Immunohistological examination revealed glomerular and tubulointerstitial expression of endostatin. Conclusion: These data suggest the local synthesis of a 30 kDa endostatin-related fragment following acute renal failure and suggest its role in the modulation of renal capillary density.

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BELLINI, MARIA H.; COUTINHO, ENIA L.; FILGUEIRAS, THELMA C.; MACIEL, THIAGO T.; SCHOR, NESTOR. Endostatin expression in the murine model of ischaemia/reperfusion-induced acute renal failure. Nephrology, v. 12, p. 459-465, 2007. DOI: 10.1111/j.1440-1797.2007.00850.x. Disponível em: http://repositorio.ipen.br/handle/123456789/5199. Acesso em: 20 Mar 2026.
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