Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Downregulation of urokinase-type and tissue-type plasminogen activators in a rabbit model of renal ischemia/reperfusion. 1220 21

Central mechanisms leading to ischemia induced allograft rejection are apoptosis and inflammation, processes highly regulated by the urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR). Recently, up-regulation of uPA and uPAR has been shown to correlate with allograft rejection in human biopsies. However, the causal connection of uPA/uPAR in mediating transplant rejection and underlying molecular mechanisms remain poorly understood. In this study, we evaluated the role of uPA/uPAR in a mice model for kidney ischemia reperfusion (IR) injury and for acute kidney allograft rejection. uPAR but not uPA deficiency protected from IR injury. In the allogenic kidney transplant model, uPAR but not uPA deficiency of the allograft caused superior recipient survival and strongly attenuated loss of renal function. uPAR-deficient allografts showed reduced generation of reactive oxygen species and apoptosis. Moreover, neutrophil and monocyte/macrophage infiltration was strongly attenuated and up-regulation of the adhesion molecule ICAM-1 was completely abrogated in uPAR-deficient allografts. Inadequate ICAM-1 up-regulation in uPAR(-/-) primary aortic endothelial cells after C5a and TNF-alpha stimulation was confirmed by in vitro experiments. Our results demonstrate that the local renal uPAR plays an important role in the apoptotic and inflammatory responses mediating IR-injury and transplant rejection.
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PMID:Renal urokinase-type plasminogen activator (uPA) receptor but not uPA deficiency strongly attenuates ischemia reperfusion injury and acute kidney allograft rejection. 1860 71