DIFFERENTIAL GENE-EXPRESSION IN THE RECOVERY FROM ISCHEMIC RENAL INJURY

Recovery from renal ischemia requires regeneration of damaged tubular epithelium. Previous studies have examined the expression of protooncogenes and growth factors after ischemia, but the response of genes coding for structural and functional genes has not been scrutinized. Rats were subjected to 40 minutes of renal artery occlusion and 60 minutes to 96 hours of reperfusion. Total RNA was isolated and mRNA for the structural protein actin, the enzymes superoxide dismutase and renin, the proto-oncogene c-fos, the nuclear protein histone H2b, and the putative marker for cell injury TRPM-2 was quantitated by Northern hybridization. Expression of the proto-oncogene c-fos was seen early but for only short duration. Histone gene expression was not markedly increased until 24 hours after ischemia, but remained increased for several days. Renin mRNA was undetectable one hour after ischemia, but was present in normal amounts at 24 and 48 hours. In contrast, superoxide dismutase mRNA was present in decreased amounts 24, 48, and 96 hours after ischemia. TRPM-2 gene expression was greatly increased 24 to 72 hours after ischemia and began decreasing at 96 hours. This selective sequence of gene expression or repression after renal ischemia might maximize the proliferative repair process. This information will be useful for designing therapies to further enhance recovery from acute renal injury.