Outcome of Acute Renal Injury in Diabetic Mice with Experimental Endotoxemia : Role of Hypoxia-Inducible Factor-1α

• Published in: Journal of diabetes research Vol. 2013; no. 2013; pp. 1 - 8
• Main Authors: García-Bermejo, L., Lucio-Cazana, J., Bosch, Ricardo J., Ortega, Arantxa, Olea, Nuria, Arribas, Ignacio, Muñóz-Moreno, C., Fernández, A., Arenas, María Isabel, López-Luna, P.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2013; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Acute Kidney Injury - complications; Acute Kidney Injury - genetics; Acute Kidney Injury - metabolism; Animals; Antibodies; Cell Line; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetic Nephropathies - complications; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Endotoxemia - complications; Endotoxemia - metabolism; Experiments; Glucose; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Kidney - metabolism; Mice; Proteins; Sepsis; Statistical analysis; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; St Louis Missouri; United States > US
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2013/254529

The role of diabetic nephropathy in the outcome of acute renal injury (AKI) is not well defined. Herein we evaluate the outcome of lipopolysaccharide- (LPS-) induced AKI in streptozotocin-induced diabetes, as well as the potential role of Hypoxia Inducible Factor (HIF-1α) in this condition. Although 6 h after LPS injection all mice developed a decrease in renal function, proteinuric diabetic mice showed a better recovery of this parameter throughout the study (72 h). Both HIF-1α and vascular endothelium growth factor (VEGF) were found to be upregulated in diabetic mice. After LPS injection, all animals showed an upregulation of these factors, although it was higher in the diabetic group. Glycated albumin (GA) was found to upregulate HIF-1α in HK-2 cells, which resulted in increased production of VEGF. Interestingly, LPS cooperated with GA to induce HIF-1α upregulation. In conclusion, diabetic mice display a better recovery of AKI after experimental endotoxemia. Moreover, these animals showed an increased expression of both HIF-1α and VEGF that was reproduced by incubating renal cells with GA. Since VEGF is considered a survival factor for tubular cells, our findings suggest that diabetes displays HIF-1α upregulation that might function as a “precondition state” offering protection from endotoxic AKI.