title: Differential gene expression following early renal ischemia/reperfusion.
abstract: BACKGROUND
  Acute renal failure from ischemia/reperfusion injury is associated with tubule cell apoptosis, the molecular mechanisms of which remain under active investigation. The purpose of this study was to identify apoptosis-related genes that are differentially expressed in the early periods following renal ischemia.
  
  
  METHODS
  Mice underwent unilateral renal artery clamping for 45 minutes and were sacrificed at 0, 3, 12, or 24 hours of reperfusion. Tubule cell apoptosis was confirmed by DNA laddering and terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. We employed cDNA microarrays to define global changes in renal gene expression. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used as confirmatory tools.
  
  
  RESULTS
  By microarray analysis, we identified consistent patterns of altered gene expression, including transcription factors, growth factors, signal transduction molecules, and apoptotic factors. Prominent among the last category included FADD, DAXX, BAD, BAK, and p53. Up-regulation of these proapoptotic genes was confirmed by semiquantitative RT-PCR and immunohistochemistry.
  
  
  CONCLUSIONS
  The results indicate that apoptosis may represent an important mechanism for the early loss of tubule cells following ischemia/reperfusion injury. Both the death receptor-dependent (FADD-DAXX) and mitochondrial (BAD-BAK) pathways are activated. The results also provide a molecular basis for the previous findings that significant intrarenal mechanisms exist to enable tubule cell repair and regeneration, as evidenced by the up-regulation of genes such as growth, proliferation, transcription, and cytoskeletal factors.
authors.affiliation: Pediatric Nephrology, Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Suroj
authors.initials: S
authors.lastname: Supavekin
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kaskel
authors.forename: Leon C
authors.initials: LC
authors.lastname: Moore
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D000818:Animals; D017209:Apoptosis; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015427:Reperfusion Injury / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation