title: Outcome of acute renal injury in diabetic mice with experimental endotoxemia: role of hypoxia-inducible factor-1 α.
abstract: 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-1 α ) 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-1 α 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-1 α in HK-2 cells, which resulted in increased production of VEGF. Interestingly, LPS cooperated with GA to induce HIF-1 α upregulation. In conclusion, diabetic mice display a better recovery of AKI after experimental endotoxemia. Moreover, these animals showed an increased expression of both HIF-1 α 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-1 α upregulation that might function as a "precondition state" offering protection from endotoxic AKI.
authors.affiliation: Laboratory of Renal Physiology and Experimental Nephrology, Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ortega
authors.forename: A
authors.initials: A
authors.lastname: Fernández
authors.forename: M I
authors.initials: MI
authors.lastname: Arenas
authors.forename: P
authors.initials: P
authors.lastname: López-Luna
authors.forename: C
authors.initials: C
authors.lastname: Muñóz-Moreno
authors.forename: I
authors.initials: I
authors.lastname: Arribas
authors.forename: N
authors.initials: N
authors.lastname: Olea
authors.forename: L
authors.initials: L
authors.lastname: García-Bermejo
authors.forename: J
authors.initials: J
authors.lastname: Lucio-Cazana
authors.forename: R J
authors.initials: RJ
authors.lastname: Bosch
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D019446:Endotoxemia / Q000150:complications / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A