Comprehensive analysis of the renal transcriptional response to acute uranyl nitrate exposure.

Background : Chemical and radiological toxicities related to uranium acute exposure have beenwidely studied in nuclear fuel workers and military personnel. It is well known that uranyl nitrateinduces acute renal failure (ARF). However, the mechanisms of this metal-induced injury are notwell defined at the molecular level. Results : Renal function and histology were assessed in mice receiving uranyl nitrate (UN(+)) andcontrols (UN(-)). To identify the genomic response to uranium exposure, serial analysis geneexpression (SAGE) of the kidney was performed in both groups. Over 43,000 mRNA SAGE tagswere sequenced. A selection of the differentially expressed transcripts was confirmed by real-timequantitative PCR and Western blotting. UN(+) animals developed renal failure and displayed thecharacteristic histological lesions of UN nephropathy. Of the >14,500 unique tags identified in bothlibraries, 224 had a modified expression level; they are known to participate in inflammation, iontransport, signal transduction, oxidative stress, apoptosis, metabolism, and catabolism. Severalgenes that were identified had not previously been evaluated within the context of toxic ARF suchas translationally controlled tumor protein, insulin like growth factor binding protein 7 andribosomal protein S29, all apoptosis related genes. Conclusion : We report a comprehensive description of the UN induced modifications in geneexpression levels, including the identification of genes previously unrelated to ARF. The study ofthese genes and the metabolisms they control should improve our understanding of toxic ARF andenlighten on the molecular targets for potential therapeutic interventions