Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vitro model of wound healing was used to study cell migration that is independent of proliferation during renal regeneration after acute tubular necrosis. Monolayer cultures of high-density, quiescent renal epithelial cells of the BSC-1 line were subjected to scrape wounding and then Northern blot analysis was employed to identify genes that mediate cell migration. After wounding the monolayer, there is maximal induction of the immediate-early genes Egr-1, c-fos, NAK-1, and gro at 1 hour, followed by peak induction of connective tissue growth factor (CTGF) and c-myc at 4 hours. Message levels of urokinase-type plasminogen activator (u-PA) and its inhibitor (PAI-1) and heat shock protein (HSP)-70 are markedly raised 4-8 hours after wounding. Constitutive expression is repressed at 1 hour for transcripts that encode receptors for fibronectin (FN), epidermal growth factor, and hepatocyte growth factor (c-met), and the secreted proteins FN and osteopontin. Expression of genes encoding transforming growth factor (TGF)-beta 1 and -beta 2, retinoic acid receptor alpha, int-1, int-2, and gap junction protein which can play a role in cell movement, appeared unchanged after wounding. Differential expression of genes was a function of cell location relative to the wound; NAK-1, PAI-1, and HSP-70 were induced or stimulated only in cells at the wound edge, u-PA was stimulated in cells away from the wound, and CTGF was induced in each of these populations suggesting that cell-to-cell communication may regulate gene expression after wounding. Adenosine diphosphate, a potent stimulator of cell migration which enhances expression of u-PA and PAI-1 in nonwounded cultures, additively stimulates these genes after wounding and may thereby potentiate wound healing. Thus scrape wounding of renal epithelial cells is followed by induction, stimulation, or repression of specific genes with distinct responses in different populations of cells.
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PMID:Differential gene expression in migrating renal epithelial cells after wounding. 759 35

Renal thrombotic microangiopathy is characterized by glomerular and vascular thrombosis. The persistancy of fibrin deposits may result from imbalance between plasminogen activation and inhibition. In the present study, we used immunohistochemistry and in situ hybridization techniques to determine the localization of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators, type 1 plasminogen activator inhibitor (PAI-1) and membrane receptor for u-PA (uPA-R) antigen and their sites of synthesis in renal thrombotic microangiopathy (N = 10) as compared to acute tubular necrosis (N = 5) and normal human kidneys (N = 7). We found an induction of PAI-1 and uPA-R expression in glomeruli and in arterial walls in renal thrombotic microangiopathy. In addition, the induction of uPA-R expression was also found in some tubular epithelial cells. In most case, local synthesis of PAI-1 and uPA-R was confirmed by in situ hybridization with the corresponding cDNA probes. In contrast, using similar techniques PAI-1 and uPA-R antigens and messenger RNAs could not be detected in normal kidneys. In both renal thrombotic microangiopathy and normal kidneys, t-PA mRNA was detected in large amounts in all glomeruli and in vascular endothelial cells, but t-PA antigen was only detected in a limited number of glomerular and arterial endothelial cells, whereas it was strongly expressed by all venous endothelial cells. Although u-PA antigen was found in almost all tubular sections, u-PA mRNA was only found in tubular epithelial cells in the deep cortex and the outer medulla. Our results indicate that there is an up-regulation of PAI-1 and u-PA-R expression in the glomeruli and in the arterial walls of thrombotic microangiopathy. The local release of PAI-1 could play a role in the persistancy of fibrin deposition and the further development of fibrotic lesions. Whether uPA-R plays a pathogenic role in the development of glomerular and vascular lesions, or is involved in the repair process of these lesion, remains to be elucidated.
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PMID:Different expression of the plasminogen activation system in renal thrombotic microangiopathy and the normal human kidney. 1178 20