Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several clinical studies have confirmed that histomorphometric changes in the tubulointerstitial compartment contain the best correlating parameters to predict the development of progressive renal insufficiency. The process of interstitial fibrosis is accompanied by an influx of inflammatory cells, up-regulation of fibrogenic cytokines such as transforming growth factor-beta and basic fibroblast growth factor, transient down-modulation of their antagonists, generation and proliferation of myofibroblasts, and, finally, by accumulation of interstitial collagens and proteoglycans. A careful morphometric analysis of interstitial fibrosis requires sensitive parameters through which the severity can be quantified and by which the progression into renal insufficiency can be predicted. We have addressed these issues by morphometric analysis of both human biopsies and by refining existing experimental models in the rat. Morphometric analysis was performed using a Zeiss microscope equipped with a full colour 3CCD camera and KS-400 image analysis software from Zeiss-Kontron. For studies with human material, biopsies were examined from patients with various renal diseases including patients with chronic allotransplant dysfunction. The development of interstitial fibrosis was correlated with clinical parameters. In experimental models, we analysed the interstitial composition and eventual glomerular alterations in rats with bovine serum albumin (BSA)-induced protein overload nephropathy and with human IgG-induced chronic serum sickness nephritis. Finally, we adapted and refined the model of ureter obstruction-induced interstitial fibrosis in the rat. For this purpose, custom-made titanium clips (S&T, Neuhaus, Switzerland) were implanted around the ureter in the abdomen of rats to obstruct the ureter without causing necrosis. The clips were removed at various time points after obstruction of the ureter (1-14 days). The subsequent remodelling of the interstitium was studied thereafter, in order to establish whether uraemia-induced interstitial fibrosis remains reversible at all times. In rat models, we have found that both protein overload-induced and serum sickness-induced interstitial fibrosis are accompanied by the development of focal and segmental glomerulosclerosis. Only in the ureter obstruction model did selective interstitial fibrosis develop, and remained reversible at all times studied. For the reliable assessment of interstitial fibrosis we have found that the best correlating parameters of interstitial fibrosis with renal function were: (i) the ratio of protein accumulation of TGF-beta-1 and its antagonist decorin; (ii) interstitial expression of smooth muscle alpha-actin; and (iii) accumulation of interstitial collagens (as determined by immunoperoxidase and by Sirius red staining).
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PMID:Morphometry of interstitial fibrosis. 1114 98

We performed differential display analysis to determine transcriptional activity in the rat kidney, following unilateral ureteral obstruction and found a 12-fold increase in the expression of Growth Arrest and DNA Damage-45gamma (GADD45gamma), a stress-responsive molecule that interacts with cell-cycle proteins. GADD45gamma was strongly expressed in as little as 6 h following ureteric obstruction in the renal tubules, and was also found in kidney tissue of patients with chronic glomerulonephritis. Adenovirus-mediated expression of GADD45gamma in cultured renal tubular cells activated p38 along with a significant upregulation of C-C and C-X3-C chemokine ligands and fibrosis-related factors such as several matrix metalloproteinases, transforming growth factor-beta1, decorin, and bone morphogenetic protein 2. Silencing of GADD45gamma expression significantly blunted the upregulation of these inflammatory and fibrogenic mediators and monocyte infiltration in the ureteral obstructed rat kidney. Our study shows that GADD45gamma is quickly upregulated in the kidney with an obstructed ureter, enhancing the production of factors regulating the pathogenesis of kidney disease.
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PMID:Upregulation and function of GADD45gamma in unilateral ureteral obstruction. 1835 78