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)

We report that activin profoundly alters epithelial branching morphogenesis of embryonic mouse salivary gland, pancreas and kidney rudiments in culture, indicating that it may play a role as a morphogen during mammalian organogenesis. In developing pancreas and salivary gland rudiments, activin causes severe disruption of normal lobulation patterns of the epithelium whereas follistatin, an activin-binding protein, counteracts the effect of activin. In the kidney, activin delays branching of the ureter bud and reduces the number of secondary branches. TGF-beta induces a pattern of aberrant branching in the ureter bud derived epithelium distinct from that seen for activin. Reverse-transcriptase polymerase chain reaction, Northern hybridization and in situ hybridization analyses indicate that these developing tissues express the mRNA transcripts for activin subunits, follistatin or activin receptors. Our results are suggestive of a potential role for the activin-follistatin system as an intrinsic regulator of epithelial branching morphogenesis during mammalian organogenesis.
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PMID:Activin disrupts epithelial branching morphogenesis in developing glandular organs of the mouse. 761 33

The rationale of the somatic gene therapy is the correction of diseases at the most fundamental level. Ideal gene therapy should be achieved by the replacement of the wrong gene sequence of genome with correct one. However, the gene technology to date is yet immature so as to correct the wrong gene sequence in vivo. Potentially, the present technology of gene transfer may provide: 1) correction of cellular dysfunction by expressing the deficient gene; 2) addition of new function for a cell by transferring an exogenous gene; 3) inhibition of unfavorable action of a cell by introducing a counteracting gene. In nephrology, the gene transfer targeted kidney has been challenged at the experimental level. HVJ-liposome method and recombinant adenovirus allow gene transfer to the particular cells in kidney in vivo. Ex vivo gene transfer using mesangial cells and macrophages are another option. Transplant kidney is also a good material for genetic engineering. The potential application of gene transfer is enormous while the therapeutic application have just begun to explored. We have been devoted to HVJ-liposome mediated gene transfer to the kidney and successfully demonstrated the suppression of the extracellular matrix accumulation of the glomeruli in the experimental glomerulonephritis through inhibition of the TGF-beta action by antisense oligonucleotides or soluble type receptor chimera for TGF-beta. We also applied this technology to the inhibition of interstitial fibrosis in unilateral ureter obstruction model. The new HVJ-liposome method improved in lipid composition allows gene transfer to tubulointerstitial fibroblast by retrograde approach from ureter. In consequence, introduced TGF-beta antisense suppressed the TGF-beta mRNA in concomitant with ameliorating interstitial fibrosis. We believe that the gene transfer technique will become common strategy to study the molecular aspect of the renal diseases and will be possibly applicable to molecular intervention in nephrology.
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PMID:Towards gene therapy for renal diseases. 985 74

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

For elucidation of the mechanisms by which growth factors and cytokines affect renal epithelial cells, gene array analysis of renal cells cultured in the presence of transforming growth factor-beta1 (TGF-beta1) was performed. Many genes that were not previously considered to be involved in renal cell biologic processes were affected, one of which was jagged-1. The jagged ligand/notch receptor family controls the formation of boundaries between groups of cells and regulates cell fates. On the basis of the array analysis, jagged-1 expression was further evaluated in cultured cells and in C57BL/6 mice with a model of unilateral ureteral obstruction (UUO). Recombinant human TGF-beta1 increased jagged-1 mRNA levels at concentrations between 10(-11) and 10(-10) M. There was a commensurate increase in jagged-1 protein levels, as assessed by Western blotting. The expression of jagged-1 mRNA and protein was observed to be significantly increased in the kidneys of C57BL/6 mice with obstructed ureters, compared with the contralateral kidneys, at 7 and 14 d of UUO. Immunohistochemical analyses demonstrated jagged-1 expression in distal tubules of kidneys from normal mice or contralateral kidneys from mice with UUO. Jagged-1 protein expression was increased in tubules not yet in apparent atrophy in the kidneys with an obstructed ureter. Jagged-1 expression was significantly increased in the kidneys of normal mice treated with TGF-beta1 and was decreased in the kidneys of mice with UUO treated with a TGF-beta receptor II-Fc chimera. These results suggest that jagged-1 is expressed in normal kidneys and that this expression is upregulated during renal disease, in a TGF-beta-dependent manner.
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PMID:Transforming growth factor-beta induces renal epithelial jagged-1 expression in fibrotic disease. 1203 79