Brain-death-induced gene regulatory networks in donor kidneys

Brain death has been shown to affect hormone regulation, hemodynamic stability and inflammatory reactivity. In transplant models, kidneys, livers and lungs retrieved from brain-dead (BD) rats do suffer from increased primary non-function and deteriorated graft survival. However, the mechanism(s) by which brain death leads to these processes have remained unclear, yet. To further unravel these mechanisms we performed DNA microarray studies with RNA isolated from kidneys from BD rats. Kidneys from sham operated animals were used as controls. Oligonucleotide arrays were manufactured using the Sigma/Genosys Rat Oligonucleotide Library harbouring 4854 unique, gene-specific rat sequences. In kidneys from normotensive donors 63 genes were identified that were either up (55) or down (8) regulated. By using PubMed searches and GeneOntology, genes were assigned to different functional clusters: Metabolism and Transport (including water channel Aqp-2), Inflammation and Coagulation (containing the largest number (16) of up regulated genes), Growth/Regeneration and Fibrosis (including genes as KIM-1 involved in tubular regeneration) and Defense and Repair (with the cytoprotective genes HO-1, Hsp70 and MnSOD2). Also genes encoding transcription factors and proteins involved in signal transduction (such as Pik3r1) were identified. In addition, Pathway AssistTM software was used for further interpretation of our microarray data in the context of pathways, gene regulatory networks and protein interactions. These type of analyses will allow us to create a better understanding of the brain-death-related biochemical pathways which are either induced or repressed. Ultimately, these approaches will help us to design specific interventions in the brain dead donor to better maintain or even repair organ viability and protect against ischemia/reperfusion injury. © 2006 by Nova Science Publishers, Inc. All rights reserved.