Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have suggested that crescents are primarily of monocytic origin and that epithelial cells are a minor factor in their composition. Frozen sections of renal biopsies from 11 cases of crescentic glomerulonephritis (CGN) and 5 controls (2 acute interstitial nephritis, 1 focal glomerulosclerosis, 1 benign recurrent hematuria, 1 normal kidney) were stained for intracellular cytokeratin (CK) with a mouse monoclonal anti-CK antiserum (PKK1) and nonspecific esterase (NSE) activity. Indirect immunofluorescence with PKK1 antiserum showed that in all biopsies there was positive staining of collecting duct and proximal and distal tubular epithelium but no reactions in blood vessels or interstitium. In control case glomeruli there was no staining of the tuft, including the visceral epithelium. In all cases some parietal epithelium was CK-positive. In 4 CGN biopsies the majority of the crescents showed cytoplasmic staining for CK in more than 50% of the crescent cells. In 2 cases most crescents contained between 10-50% CK-positive cells, whereas in 5 biopsies little or no CK was present in the majority of crescents. In all but one CGN case the majority of crescents contained fewer than 30% NSE-positive cells (monocytes). Electron microscopy demonstrated intermediate filaments in many crescent cells and scattered desmosomes within crescents. The results indicate that epithelial cells, probably of parietal epithelial origin, contribute significantly to crescent formation.
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PMID:Histogenesis of glomerular crescents. Immunohistochemical demonstration of cytokeratin in crescent cells. 241 Nov 41

Renal failure was diagnosed in 22 young Doberman Pinscher dogs. The clinical findings were anorexia, weight loss, vomiting, lethargy, polydipsia, polyuria, and dehydration. Laboratory findings were azotemia, hyperphosphatemia, lymphopenia, nonregenerative anemia, hypercholesterolemia, and proteinuria. The kidneys were characterized pathologically by glomerular sclerosis, cystic glomerular atrophy, tubular dilatation, tubular atrophy, mononuclear interstitial inflammation, interstitial fibrosis, interstitial mineralization, and hyperplasia of the collecting duct epithelium.
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PMID:Juvenile renal disease in Doberman Pinscher dogs. 683 84

Alterations in the renal metabolism and/or actions of endothelin-1 (ET-1) may be involved in the pathogenesis and maintenance of essential and renal parenchymal hypertension. ET-1 has the potential to modify a broad range of renal functions involved in controlling systemic blood pressure. First, the kidney clears a large percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute to hypertension occurring in the setting of chronic renal failure. Second, ET-1 potently constricts the renal vasculature resulting in increased fluid retention and possibly contributing to glomerular sclerosis; enhanced renal vascular and glomerular ET-1 production and target cell actions may play a role in essential hypertension or hypertension accompanying chronic renal failure, cyclosporine administration, or erythropoietin therapy. Lastly, ET-1 is also an autocrine inhibitor of collecting duct sodium and water reabsorption; reduced nephron ET-1 production may result in fluid retention in essential hypertension. Determination of the true role that ET-1 plays in the pathogenesis of the varied forms of hypertension awaits the development of safe, potent, and specific endothelin antagonists.
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PMID:Role of intrarenal endothelin in the generation and maintenance of hypertension. 756 83

The ability to control body hydration is frequently impaired with age. This mainly results from changes in thirst and from loss of renal concentrating ability. The cellular mechanisms responsible for this functional renal failure have been extensively studied in different experimental models. Although the loss of nephrons sometimes observed with age impairs the ability of the kidney to retain water, a similar defect was reported in animals free of glomerulosclerosis, indicating that the reduction in the number of nephrons was not the only cause. Because age-related polyuria has also been demonstrated in rats with unchanged secretion of vasopressin, renal changes in water reabsorption was hypothesized. Such alterations have been searched along the whole length of the nephron. Neither the single nephron filtration rate nor proximal or early distal flow rates were modified in senescent animals where water reabsorption in the collecting duct was reduced. The affinity and the density of the V2 receptors were mainly constant in most experimental models of ageing. In contrast, intracellular cAMP accumulation following vasopressin stimulation was reduced in the oldest animals. The expression of aquaporins in luminal and basolateral membranes of the collecting duct epithelial cells was altered. The amount of basolateral aquaporin 3 and 4 was respectively decreased by 50 per cent and unchanged in renal papilla. In addition, the expression of aquaporin 2, which is rate limiting for the osmotic permeability of the collecting duct, was reduced by 50 per cent in the outer medulla and by 80 per cent in the inner medulla of the senescent animals. This drop in aquaporin 2 expression in the distal part of the nephron could be the main cause for the fall in concentrating ability of the kidney and the age-related impaired control of hydration.
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PMID:[Kidney aging: cellular mechanisms of problems of hydration equilibrium]. 1021 38

Morphological study of the kidney is generally the first step in the diagnosis of Alport's syndrome. Light microscopy study allows to suggest the diagnosis with the association of focal and segmental glomerulosclerosis, GBM anomalies when studied with silver staining, interstitial foam cells, and negative standard immunofluorescence study. GBM anomalies observed by electron microscopy are nearly specific with thickening splitting and fragmenting of the lamina densa. GBM anomalies are the consequence of a collagen IV disease. Thus, immunohistochemical results obtained with 6 different alpha(IV) are essential and allow to evaluate the mode of inheritance. Schematically, in the X dominant AS form, GBM, distal tubular BM and collecting duct BM do not express alpha3/alpha4, alpha5(IV). In the autosomic recessive AS form, collecting duct BM alone express alpha5(IV) without expression of alpha3(IV) and alpha5(IV) chains along the GBM and distal TBM.
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PMID:Renal pathology and ultrastructural findings in Alport's syndrome. 1110 62

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Three PPAR isoforms, designated PPAR-alpha, beta/delta and -gamma, have been identified and were initially investigated in the tissues along urinary tract because of their known role in regulating lipid-activated gene transcription, lipid metabolism, inflammation and cell proliferation and differentiation. Gene distribution studies suggested that 3 PPAR isoforms are differentially expressed in the kidney. PPAR-alpha is predominantly expressed in renal proximal tubules and medullary thick ascending limbs. PPAR-gamma is mainly localized in renal medullary collecting duct with lower expression in renal glomeruli and renal microvasculature. Unlike PPAR-alpha and -gamma, PPAR-beta/delta is ubiquitously expressed in every segment along the nephron. In ureter and urinary bladder, all PPAR isoforms are mainly localized in urothelium of ureter and bladder. The emerging data have suggested physiological and pathophysiological roles of PPARs in tissues along urinary tract. PPAR-alpha plays a major role in triggering fatty acid utilization and the adaptive response to dietary lipids in the kidney. PPAR-beta/delta contributes to cell survival of renal interstitial cell in medullary hyperosmality. PPAR-gamma is involved in regulating renal hemodynamic and water and sodium transport. Furthermore, it also participates in the pathogenesis of glomerulopathy, antidiabetic thiazolidinedione-related water and sodium retention and renal, bladder and prostate carcinomas. PPARs may serve as potential therapeutic targets for certain diseases along urinary tract including glomerulosclerosis, diabetic nephropathy and kidney, prostate and bladder tumors.
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PMID:Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and urologic disease. 1218 90

Adrenomedullin (AM) is a potent vasodilatory peptide originally discovered in human pheochromocytoma tissue. AM and AM gene expression are widely distributed in the cardiovascular system, including the kidney. The co-localization of AM and its receptor components such as calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP)2 and RAMP3 in the kidney, heart, and vasculature suggests an important role for the peptide as a regulator of renal, cardiac, and vascular function. Indeed, in addition to its cardiovascular effects, AM has renal vasodilatory, natriuretic, and diuretic actions. Consistent with these observations, immunohistochemical studies revealed that AM is stained in the collecting duct, distal convoluted tubules, vessels, and glomerular mesangial cells, endothelial cells and podocytes. Plasma AM levels are increased in patients with renal impairment in proportion to the severity of the disease. Previously we and other investigators showed that two molecular forms of AM, AM-glycine, an inactive form, and AM-mature, an active form, circulate in human plasma. Urine also contains both forms of AM; however, the AM-mature/AM-glycine ratio is higher in urine than in plasma. Interestingly, plasma AM-glycine and AM-mature levels are increased in renal failure, whereas urinary AM-glycine and AM-mature are decreased in this condition. These results indicate that the origin of urinary AM is different from that of plasma AM. Experimental studies showed that the renal tissue AM-mature/AM-glycine ratio is higher than that in plasma and urine. In addition, renal tissue concentrations of AM are increased in severely hypertensive rats. Considering that AM has antiapoptotic, antifibrotic, and antiproliferative effects, the increase of AM in renal disease may be a protective mechanism. In fact, AM gene delivery or long-term AM infusion significantly improved glomerular sclerosis, interstitial fibrosis, and renal arteriosclerosis in several malignant hypertensive models. This review describes the biochemistry, physiology, and circulating levels of AM and also discusses what is known about the pathophysiological role of AM in renal disease.
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PMID:Adrenomedullin in the kidney-renal physiological and pathophysiological roles. 1758 73

Hyperfiltration occurs in early type 1 diabetes mellitus in both rats and humans. It results from afferent vasodilation and thus may impair stabilization of glomerular capillary pressure by autoregulation. It is inversely related to dietary salt intake, the "salt paradox." Restoration of normal glomerular filtration rate (GFR) involves increased preglomerular resistance, probably mediated by tubuloglomerular feedback (TGF). To begin to test whether the salt paradox has pathogenic significance, we compared intact vs. diabetic (streptozotocin) Long-Evans rats with normal and increased salt intake, 1 and approximately 3% by weight of food eaten, respectively. Weekly 24-h blood pressure records were acquired by telemetry before and during diabetes. Blood glucose was maintained at approximately 20 mmol/l by insulin implants. GFR was significantly elevated only in diabetic rats on normal salt intake, confirming diabetic hyperfiltration and the salt paradox. Renal blood flow dynamics show strong contributions to autoregulation by both TGF and the myogenic mechanism and were not impaired by diabetes or by increased salt intake. Separately, systolic pressure was not elevated in diabetic rats at any time during 12 wk with normal or high salt intake. Autoregulation was effective in all groups, and the diabetic-normal salt group showed significantly improved autoregulation at low perfusion pressures. Histological examination revealed very minor glomerulosclerosis and modest mesangial expansion, although neither was diagnostic of diabetes. Periodic acid-Schiff-positive droplets found in distal tubules and collecting duct segments were diagnostic of diabetic kidneys. Biologically significant effects attributable to increased salt intake were abrogation of hyperfiltration and of the left shift in autoregulation in diabetic rats.
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PMID:Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes. 1933 76

Connective tissue growth factor (CTGF) participates in diverse fibrotic processes including glomerulosclerosis. The adenylyl cyclase agonist forskolin inhibits CTGF expression in mesangial cells by unclear mechanisms. We recently reported that the histone H3K79 methyltransferase disruptor of telomeric silencing-1 (Dot1) suppresses CTGF gene expression in collecting duct cells (J Clin Invest 117: 773-783, 2007) and HEK 293 cells (J Biol Chem In press). In the present study, we characterized the involvement of Dot1 in mediating the inhibitory effect of forskolin on CTGF transcription in mouse mesangial cells. Overexpression of Dot1 or treatment with forskolin dramatically suppressed basal CTGF mRNA levels and CTGF promoter-luciferase activity, while hypermethylating H3K79 in chromatin associated with the CTGF promoter. siRNA knockdown of Dot1 abrogated the inhibitory effect of forskolin on CTGF mRNA expression. Analysis of the Dot1 promoter sequence identified a CREB response element (CRE) at -384/-380. Overexpression of CREB enhanced forskolin-stimulated Dot1 promoter activity. A constitutively active CREB mutant (CREB-VP16) strongly induced Dot1 promoter-luciferase activity, whereas overexpression of CREBdLZ-VP16, which lacks the CREB DNA-binding domain, abolished this activation. Mutation of the -384/-380 CRE resulted in 70% lower levels of Dot1 promoter activity. ChIP assays confirmed CREB binding to the Dot1 promoter in chromatin. We conclude that forskolin stimulates CREB-mediated trans-activation of the Dot1 gene, which leads to hypermethylation of histone H3K79 at the CTGF promoter, and inhibition of CTGF transcription. These data are the first to describe regulation of the Dot1 gene, and disclose a complex network of genetic and epigenetic controls on CTGF transcription.
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PMID:CREB trans-activation of disruptor of telomeric silencing-1 mediates forskolin inhibition of CTGF transcription in mesangial cells. 2005 91

Sickle cell disease (SCD), the first 'molecular disease' to be identified, has been well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. Thus, the manifestations of SCD chronic renal disease have long been considered clinical manifestations of an obstructive vasculopathy of the arterial and capillary microcirculation. Recently, accumulating evidence have indicated that blood vessel functions are affected by SCD, involving abnormal vascular tone and activated endothelium. These abnormalities are particularly prominent in the kidney where specific biochemical conditions in the medulla and papilla favor change in endothelial phenotype and in tubular phenotype that, in turn, may promote dysfunction and destruction of this organ through active endothelin (ET)-1 production and signals. High ET-1 urinary output in SCD subjects at steady state may reflect increased tubular activation of ET-1 production acting on the collecting duct thereby favoring the constant hyposthenuria. Chronically, augmented ET-1 concentrations in the SCD kidney would further aggravate ischemia and sickling through actions on vasa recta and red blood cells. The kidneys suffer multiple ischemic hits during SCD as consequences of vasos-occlusive crisis (VOC). Blockade of ET receptors unraveled the major vasoconstrictive role of ET-1 in the pathophysiology of VOC, stressing the pivotal role of abnormal endothelial phenotype in this hemoglobinopathy and opening potential new therapeutic options. At last, indirect evidence suggest that ET-1 may be involved in the progression of chronic glomerulosclerosis affecting a number of patients. In fact, sickle cell nephropathy is an emerging severe disease that requires pathophysiological studies and development of specific therapies.
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PMID:Endothelin in renal injury due to sickle cell disease. 2189 99


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