Background/Objective: Renal ischemia-hypoxia is a leading cause of acute kidney injury (AKI). Ischemia causes extracellular matrix breakdown of the tubular basement membrane. Endostatin (ES) is the C-terminal fragment of collagen XVIII generated by proteolytic cleavage. Recent studies have demonstrated that ES expression is upregulated in ischemic kidneys. The present study aimed to characterize ES from ischemic kidneys. Methods: Ischemic renal failure was induced via 45 min of occlusion of the left renal artery and vein. After the ischemic period, blood was collected. Kidneys were harvested and used for immunohistochemical testing and protein extraction. Three-step purification was used. Soluble and immobilized purified ES were tested in cell viability and adhesion assays. Results: The soluble KES28 kDa inhibited endothelial cell proliferation: 25 versus 12.5 µg (p < 0.05); 12.5 versus 3.15 µg (p < 0.05). Immobilization of KES28 kDa supports endothelial cell survival over the control (p = 0.021). Human umbilical vein endothelial cells plated on immobilized KES28 kDa showed an increase in membrane ruffles and stress fibers. Conclusion: These data demonstrate the local synthesis of a 28-kDa ES-related fragment following AKI and suggest its role in endothelium survival.

Keywords:
Acute kidney injury, Endostatin, Endothelial cell survival, Human umbilical vein endothelial cells, KES28 kDa
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2010
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