Downregulation of urokinase-type and tissue-type plasminogen activators in a rabbit model of renal ischemia/reperfusion.

Urokinase-type and tissue-type plasminogen activators (uPA, tPA) are key enzymes for starting the plasminogen system, which plays important roles in various physiological and pathological conditions. In order to examine the gene regulation in rabbit pathophysiological models we attempted to clone full-length cDNAs encoding uPA and tPA from kidney extracts of rabbit (Oryctolagus cuniculus) by reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. The cloned rabbit uPA and tPA cDNAs were 2,350 and 2,561 bp in length, respectively, and the basic molecular structures predicted from the cDNAs were well-conserved compared with human uPA and tPA. In a rabbit model of renal ischemia/reperfusion (I/R), the expression of uPA and tPA mRNAs was down-regulated and that of their physiological inhibitor, type 1 plasminogen activator inhibitor, mRNA was up-regulated in ischemic kidney compared to non-ischemic kidney. In addition, fibrinolytic activity in ischemic kidney was lower than that in non-ischemic kidney. It is suggested that repression of fibrinolysis in the kidneys in rabbit I/R may contribute to the progression of renal damage in the model.

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