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

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

Hepatocyte growth factor and its receptor, Met, activate biological pathways necessary for repair and regeneration following kidney injury. The Met receptor is expressed in multiple cell types within the kidney, each of which is capable of regulating fibrotic responses. To specifically address the role of the Met receptor in the adult collecting duct during renal injury, a conditional knockout mouse (Met(fl/fl);HoxB7-Cre) was generated and tested using unilateral ureteral obstruction, a model of nephron injury, fibrosis, and repair. Following obstruction in these mice there was increased expression of collagens I and IV along with plasminogen activator inhibitor 1, a known regulator of matrix degradation, compared to ureteral obstructed non-flox littermates. There were trends toward increased interstitial fibrosis, infiltration of the interstitium, and acute tubular necrosis in the knockout mice despite similar degrees of hydronephrosis to the control littermates. The Met(fl/fl);HoxB7-Cre mice; however, had reduced tubular cell proliferation and kidney regenerative capacity after release of the obstruction, thus leading to diminished functional recovery. We suggest that Met receptor signaling in the collecting duct acts as a major regulator of cell survival and propagation of the repair process with a possible secondary role to diminish inflammatory and fibrotic responses.
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PMID:Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction. 1967 27