%0 Journal Article
%T Outcome of Acute Renal Injury in Diabetic Mice with Experimental Endotoxemia: Role of Hypoxia-Inducible Factor-1¦Á
%A A. Ortega
%A A. Fern¨¢ndez
%A M. I. Arenas
%A P. L¨®pez-Luna
%A C. Mu£¿¨®z-Moreno
%A I. Arribas
%A N. Olea
%A L. Garc¨ªa-Bermejo
%A J. Lucio-Cazana
%A R. J. Bosch
%J Journal of Diabetes Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/254529
%X 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¦Á) 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¦Á 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¦Á in HK-2 cells, which resulted in increased production of VEGF. Interestingly, LPS cooperated with GA to induce HIF-1¦Á 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¦Á 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¦Á upregulation that might function as a ¡°precondition state¡± offering protection from endotoxic AKI. 1. Introduction The role of diabetes in the outcome of acute renal injury (AKI) is not well understood and may depend upon the cause of the injury as well as on the stage of diabetic renal involvement. Among the various causes of AKI, endotoxemia, a major component of sepsis, remains an elusive and challenging condition which is still lacking treatment. Although it is known that rodents with experimental diabetes are protected from certain nephrotoxic agents [1¨C3], diabetes has been recognized as an independent risk factor for the development of AKI in a variety of clinical settings, including sepsis [4¨C8]. Hypoxia-inducible factor (HIF-1¦Á) allows the adaptive response to hypoxia by stimulating the expression of target genes such as erythropoietin, enzymes involved in glucose metabolism, and the vascular endothelial growth factor A (VEGF-A) [9]. The later has been recognized as a survival factor for proximal tubular cells [10]. HIF-1¦Á is a heterodimer transcription factor consisting of a constitutively expressed ¦Â subunit and two ¦Á subunits, HIF-1¦Á or HIF-2¦Á. In normoxia, HIF-1¦Á is continuously synthesized but rapidly ubiquitinated and subsequently degraded by the cellular proteasome [11]. Under hypoxia, the HIF-1¦Á ubiquitination is suppressed. HIF-1¦Á
%U http://www.hindawi.com/journals/jdr/2013/254529/