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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Distinct patterns of cell proliferation and apoptosis have been recognized for tubular, interstitial, and glomerular cells in chronic obstructive uropathy (OU). In many experimental models of OU, tubular cell apoptosis develops quickly after ureter ligation, peaks between 7 and 24 days postobtruction (about 30-fold of control), and tapers thereafter. Apoptosis initially involves the dilated collecting ducts, but subsequently spreads to other tubules. Tubular cell apoptosis probably accounts for renal tissue loss in OU because a direct correlation between its degree and the decline in dry kidney weight is well-documented. Pronounced tubular cell proliferation occurs shortly after ureter ligation, peaks at about day 6 (60-fold above control), and quickly subsides to baseline. Because the peak of tubular cell proliferation immediately precedes the onset of tubular cell apoptosis, a pathogenetic link may exist between these two processes. Interstitial cell apoptosis occurs with an increasing frequency throughout the course of OU (up to 35-fold above control). Interstitial cell proliferation appears in a bimodal pattern with the early peak coinciding with that of tubular cell proliferation and consisting mostly of fibroblasts, whereas the later peak consists mostly of inflammatory cells. Glomerular cell apoptosis and proliferation are not different from control, which explains, in part, the structural integrity of the glomeruli throughout the disease course. Although the general pathways of cell apoptosis and proliferation are well known, the molecular control of these processes in OU is poorly understood. In addition, whether apoptosis or proliferation of tubular and interstitial cells is differentially regulated remains to be studied. However, several molecules known to be activated or overexpressed in kidney with OU may modulate cell apoptosis and proliferation. The relevant functions of these molecules include induction of apoptosis (angiotensin II, reactive oxygen species, jun-N-terminal kinase, p53), inhibition of the cell cycle (transforming growth factor-beta, p21), inhibition of apoptosis (clusterin, epidermal growth factor, insulin-like growth factor, bcl-2, osteopontin), or promotion of interstitial fibroblast proliferation (platelet-derived growth factor).
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PMID:Cell apoptosis and proliferation in obstructive uropathy. 981 55

BMP-7, a member of the bone morphogenic protein subfamily (BMPs) of the transforming growth factor-beta superfamily of secreted growth factors, is abundantly expressed in the fetal kidney. The precise role of this protein in renal physiology or pathology is unknown. A cDNA that encodes rat BMP-7 was cloned and used as a probe to localize BMP-7 mRNA expression by in situ hybridization in the adult rat kidney. The highest expression of BMP-7 mRNA could be seen in tubules of the outer medulla. In glomeruli, a few cells, mainly located at the periphery of the glomerular tuft, showed specific and strong signals. Also, high BMP-7 mRNA expression could be localized to the adventitia of renal arteries, as well as to the epithelial cell layer of the renal pelvis and the ureter. Preliminary evidence suggests that BMP-7 enhances recovery when infused into rats with ischemia-induced acute renal failure. We examined BMP-7 mRNA expression in kidneys with acute renal failure induced by unilateral renal artery clamping. BMP-7 mRNA abundance as analyzed by solution hybridization was reduced in ischemic kidneys after 6 and 16 h of reperfusion compared with the contralateral kidney. In situ hybridization in ischemic kidneys showed a marked decrease of BMP-7 mRNA in the outer medulla and in glomeruli. Utilizing rat metanephric mesenchymal cells in culture, we also demonstrate that BMP-7 induces epithelial cell differentiation. Taken together, these data suggest that BMP-7 is important in both stimulating and maintaining a healthy differentiated epithelial cell phenotype.
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PMID:Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney. 1007 Jan 61

Ureteral obstruction (UO) is one of the most common problems confronting the urologist. Although large amounts of animal and clinical research have been done, the pathophysiologic mechanisms accompanying UO are not fully elucidated. Most of our knowledge on UO has been derived from experimental studies in a variety of animal models. Both antenatal and postnatal UO models have been developed mainly by ligation of the ureter or by burying the ureter into the psoas muscle. Most experimental studies have focused on short-term complete ureteral obstruction. The long-term effects of partial ureteral obstruction have been less intensively studied. It is now clear that obstructive nephropathy is not a simple result of mechanical impairment to urine flow but a complex syndrome resulting in alterations of both glomerular hemodynamics and tubular function caused by the interaction of a variety of vasoactive factors and cytokines that are activated in response to UO. Leukocyte infiltration appears to play an important role in obstructive nephropathy suggesting that UO also has an immunological component. Growth factors such as platelet-derived growth factor, transforming growth factor-beta, epidermal growth factor and insulin-like growth factor I may all play a role in the development and progression of fibrotic and sclerotic changes in the obstructed kidney. At present, the selection of patients with congenital hydronephrosis for operative treatment is controversial. Studies in animals and patients have shown that partial unilateral UO does not always cause a loss of renal function or progression in urinary tract dilation during long-term follow-up. The implications of UO continue to raise many questions and further work is necessary to achieve a better understanding of the pathogenesis in obstructive nephropathy.
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PMID:Obstructive nephropathy: an update of the experimental research. 1009 51

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

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. It has been shown that the renin-angiotensin system plays a central role in the progression of interstitial fibrosis. Recent studies indicate that endothelin, a powerful vasoconstrictive peptide, may play an important role in some types of renal disease. To investigate the effects of angiotensin II on endothelin and its receptors in the kidney, mice were subjected to UUO and treated with or without enalapril, an orally active angiotensin-converting enzyme inhibitor, in their drinking water (100 mg/l). The animals were killed 5 days later. Using RT coupled with PCR, we measured the levels of endothelin-1, endothelin A, and endothelin B (ET(B)) along with transforming growth factor-beta, TNF-alpha, and collagen type IV mRNA expression in the kidney with UUO and the contralateral kidney along with interstitial expansion in the kidney cortex by a standard point counting method. We found that enalapril administration ameliorated the increased expression of ET-1 mRNA in the obstructed kidney by 44% (P < 0.02). Although the level of endothelin A mRNA expression was significantly increased in the obstructed kidney, it was not affected by enalapril. We found that enalapril treatment increased ET(B) mRNA expression by 115% (P < 0.05) and protein expression (measured by Western blot) in the kidney with an obstructed ureter. Enalapril treatment alone inhibited the expansion of interstitial volume due to UUO by 52%. Cotreatment with enalapril and the ET(B) receptor antagonist BQ-788 inhibited the expression of interstitial volume by only 19%. This study confirms that enalapril inhibits the interstitial fibrosis in UUO kidneys. It also suggests a beneficial and unforeseen effect of enalapril on the obstructed kidney by potentially stimulating the production of nitric oxide through an increased expression of the ET(B) receptor.
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PMID:ACE inhibition increases expression of the ETB receptor in kidneys of mice with unilateral obstruction. 1247 37

The objective of this study is to increase the transfection efficiency of a plasmid DNA expressing small interference RNA (siRNA) for transforming growth factor-beta receptor (TGF-betaR) by various cationized gelatins of non-viral carrier and evaluate the anti-fibrotic effect with a mouse model of unilateral ureteral obstruction (UUO). Ethylenediamine, putrescine, spermidine or spermine was chemically introduced to the carboxyl groups of gelatin for the cationization. The plasmid DNA of TGF-betaR siRNA expression vector with or without complexation of each cationized gelatin was injected to the left kidney of mice via the ureter to prevent the progression of renal fibrosis of UUO mice. Irrespective of the type of cationized gelatin, the injection of plasmid DNA-cationized gelatin complex significantly decreased the renal level of TGF-betaR over-expression and the collagen content of mice kidney, in marked contrast to free plasmid DNA injection. It is concluded that retrograde injection of TGF-betaR siRNA expression vector plasmid DNA complexed with the cationized gelatin is available to suppress the progression of renal interstitial fibrosis.
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PMID:Enhanced anti-fibrotic activity of plasmid DNA expressing small interference RNA for TGF-beta type II receptor for a mouse model of obstructive nephropathy by cationized gelatin prepared from different amine compounds. 1637 54

Nestin is an intermediate filament protein originally identified in neuroepithelial stem cells. This cytoskeletal-associated protein is also expressed in some non-neuronal organs including renal tubular cells and glomerular endothelial cells during kidney development. Little is known, however, about nestin expression in the kidney during injury. In this study, we find nestin expression induced in renal tubular and interstitial myofibroblasts in the adult rat kidney following unilateral ureteral obstruction. The degree of nestin expression was well correlated with the degree of tubulointerstitial fibrosis. Immunohistochemical identification of specific nephron segments showed that nestin was primarily expressed by proximal tubules, partially by distal tubules and thick ascending limbs of Henle but not by collecting ducts. The nestin-positive tubular cells also expressed vimentin and heat-shock protein 47 (HSP47) suggesting these cells reverted to a mesenchymal phenotype. Not all vimentin- or HSP-expressing cells expressed nestin; however, suggesting that nestin is distinct from these conventional mesenchymal markers. Nestin expression was also found associated with phenotypical changes in cultured renal cells induced by hypoxia or transforming growth factor-beta. Nestin expression was located in hypoxic regions of the kidney with an obstructed ureter. Our results indicate that nestin could be a novel marker for tubulointerstitial injury.
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PMID:Nestin expression in the kidney with an obstructed ureter. 1765 33

Systemic administration of the potent vasodilating peptide adrenomedullin reduces cardiac and renal fibrosis in hypertensive animals. Here, we investigated the effects of kidney-specific adrenomedullin gene delivery in normotensive rats after unilateral ureteral obstruction, an established model of renal tubulointerstitial fibrosis. Overexpression of exogenous adrenomedullin in the renal interstitium following ureteral obstruction significantly prevented fibrosis and proliferation of tubular and interstitial cells. In this model, there is upregulation of connective tissue growth factor (CTGF) mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation, and adrenomedullin overexpression suppressed both of these activities without altering the blood pressure. In NRK-49F renal fibroblasts, adrenomedullin reduced transforming growth factor-beta-induced CTGF and fibronectin mRNA upregulation through the cyclic AMP/protein kinase A signaling pathway, and suppressed ERK phosphorylation and cell proliferation. In the kidneys with an obstructed ureter, adrenomedullin receptor gene expression was upregulated along with cyclic AMP production in kidney slices. The latter effect was partially blocked by a neutralizing antibody to adrenomedullin, indicating that an endogenous peptide-receptor system was activated. Our results show that overexpression of exogenous adrenomedullin in the ureteral-obstructed kidney prevents tubulointerstitial fibrosis and cell proliferation through the cyclic AMP-mediated decrease of CTGF induction and ERK phosphorylation.
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PMID:Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis. 1840 34