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)

The object of this experimental study is to elucidate the limits of recovery in hydronephrosis. Hydronephrosis in the rabbit kidney was made by left ureteric ligation for 1, 2, 3 and 4 weeks, followed by relief of obstruction with uretero-ureteric anastomosis. Two and 4 weeks after relief, histopathological examination was performed. In proportion to the obstructive period, both proximal tubule and thin portion of Henle's loop showed atrophy of epithelial cells, multi-laminar thickening of basement membranes, and splitting between epithelium and basement membranes. The interstitium showed edema and subsequent fibrosis. These damages were thought to be due to severe ischemia, which such tubules did not recover and even showed more advanced damages after relief. On the other hand, thick portion of Henle's loop, distal tubule and collecting duct showed advanced compression atrophy and dilated lumen, while no severe ischemic damage was demonstrated. Therefore, after relief, they showed recovery, and, even in the case of no recovery, they showed no advanced damages. In hydronephrosis, severe ischemic damages brought about a loss of the ability of recovery.
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PMID:[The limits of recovery in hydronephrosis. An experimental pathological study]. 149 99

Regional localization of the exaggerated prostaglandin E2 (PGE2) synthesis caused by hydronephrosis was studied in unilateral ureteral ligated rabbits. The renal distribution of PGE2 production was compared in the hydronephrotic and contralateral kidneys. Basal and bradykinin-stimulated PGE2 synthesis were increased in cortical and medullary slices of the hydronephrotic kidneys. Contralateral (control) cortical slices produced very low levels of PGE2 and were insensitive to stimulation by bradykinin (BK). The hydronephrotic cortex produced 10 times more PGE2 than the contralateral cortex and responded to BK stimulation with increased PGE2 synthesis. Cortical slices from the hydronephrotic kidney exhibited a time-dependent increase in PGE2 release, presumably as a result of new protein synthesis. The division of the hydronephrotic cortex into outer and inner regions revealed that the inner cortex produced more PGE2 than the outer cortex. A similar division of the hydronephrotic medulla showed that the inner medulla produced slightly greater amounts of PGE2 than the outer medulla. The present study demonstrates that hydronephrosis causes increases in prostaglandin synthesis throughout the kidney. We suggest from these results and other studies that a possible explanation for this finding is the involvement of the collecting duct system in this response. The gradient of PGE2 production detected in the cortex may have a very significant role in the control of renal hemodynamics and could provide an explanation for the large decrease in blood flow to the inner cortex caused by indomethacin treatment.
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PMID:Localization of exaggerated prostaglandin synthesis associated with renal damage. 695 Apr 62

Aquaporin (AQP) water channel AQP3 has been proposed to be the major glycerol and non-AQP1 water transporter in erythrocytes. AQP1 and AQP3 are also expressed in the kidney where their deletion in mice produces distinct forms of nephrogenic diabetes insipidus. Here AQP1/AQP3 double knockout mice were generated and analyzed to investigate the functional role of AQP3 in erythrocytes and kidneys. 53 double knockout mice were born out of 756 pups from breeding double heterozygous mice. The double knockout mice had reduced survival and impaired growth compared with the single knockout mice. Erythrocyte water permeability was 7-fold reduced by AQP1 deletion but not further reduced in AQP1/AQP3 null mice. AQP3 deletion did not affect erythrocyte glycerol permeability or its inhibition by phloretin. Daily urine output in AQP1/AQP3 double knockout mice (15 ml) was 9-fold greater than in wild-type mice, and urine osmolality (194 mosm) was 8.4-fold reduced. The mice remained polyuric after DDAVP administration or water deprivation. The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-filled due to the severe polyuria and hydronephrosis. Our data provide direct evidence that AQP3 is not functionally important in erythrocyte water or glycerol permeability. The renal function studies indicate independent roles of AQP1 and AQP3 in countercurrent exchange and collecting duct osmotic equilibration, respectively.
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PMID:Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3. 1103 42

The ROMK (Kir1.1; Kcnj1) gene is believed to encode the apical small conductance K(+) channels (SK) of the thick ascending limb (TAL) and cortical collecting duct (CCD). Loss-of-function mutations in the human ROMK gene cause Bartter's syndrome with renal Na(+) wasting, consistent with the role of this channel in apical K(+) recycling in the TAL that is crucial for NaCl reabsorption. However, the mechanism of renal K(+) wasting and hypokalemia that develop in individuals with ROMK Bartter's syndrome is not apparent given the proposed loss of the collecting duct SK channel. Thus, we generated a colony of ROMK null mice with approximately 25% survival to adulthood that provides a good model for ROMK Bartter's syndrome. The remaining 75% of null mice die in less than 14 days after birth. The surviving ROMK null mice have normal gross renal morphology with no evidence of significant hydronephrosis, whereas non-surviving null mice exhibit marked hydronephrosis. ROMK protein expression was absent in TAL and CCD from null mice but exhibited normal abundance and localization in wild-type littermates. ROMK null mice were polyuric and natriuretic with an elevated hematocrit consistent with mild extracellular volume depletion. SK channel activity in TAL and CCD was assessed by patch clamp analysis in ROMK wild-type ROMK(+/+), heterozygous ROMK(+/-), and null ROMK(-/-) mice. In 313 patches with successful seals from the three ROMK genotypes, SK channel activity in ROMK (+/+ and +/-) exhibited normal single channel kinetics. The expression frequencies are as follows: 67 (TAL) and 58% (CCD) in ROMK(+/+); about half that of the wild-type in ROMK(+/-), being 38 (TAL) and 25% (CCD); absent in both TAL or CCD in ROMK(-/-) between 2 and 5 weeks in 15 mice (61 and 66 patches, respectively). The absence of SK channel activity in ROMK null mice demonstrates that ROMK is essential for functional expression of SK channels in both TAL and CCD. Despite loss of ROMK expression, the normokalemic null mice exhibited significantly increased kaliuresis, indicating alternative mechanisms for K(+) absorption/secretion in the nephron.
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PMID:Absence of small conductance K+ channel (SK) activity in apical membranes of thick ascending limb and cortical collecting duct in ROMK (Bartter's) knockout mice. 1213 Jun 53

L1, a member of the immunoglobulin superfamily, is a cell adhesion and signal transducing molecule. In the kidney, L1 is expressed in the mesonephric duct and the metanephros throughout collecting duct development. We show that mice with a targeted deletion of the L1 gene display diverse renal malformations including (i) a duplex kidney with two ureters partially or totally separated, accompanied by hydronephrosis; and (ii) an enlarged elongated kidney with a malformed or incorrectly positioned inner medulla. The type, penetrance and severity of these phenotypes are influenced by the genetic background. The development of a duplex kidney is initiated by double ureteral budding from the Wolffian duct or by an accessory budding from the main ureter, whereas medullary malformation is due to an improper growth and branching pattern of ureteral branches. Multiple developmental defects in formation of the collecting system promote subsequent renal damage and progression to renal insufficiency. Various features of mouse ureteral duplication resemble the human congenital anomalies of the kidney and urinary tract (CAKUT) although disturbances of medulla development have not yet been reported in men.
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PMID:Abnormal renal phenotype in L1 knockout mice: a novel cause of CAKUT. 1238 85

We report a case of Bellini duct carcinoma with giant hydronephrosis. A 56-year-old man was referred with the chief complaint of gross hematuria. The intravenous pyelography showed a huge right renal contour and non-functioning kidney. The abdominal computed tomographic scan and magnetic resonance imaging demonstrated giant hydronephrosis. Percutaneous urinary cytology obtained in the direct pyelography was class V. Right total nephro-ureterectomy was performed. Punctured fluid volume was 1,010 ml during the operation. Histological and immunohistochemical analysis revealed the collecting duct carcinoma of the kidney. Three months later, multiple bone metastases had appeared. He was treated by the combination chemotherapy of gemcitabine and paclitaxel, but lung and liver metastases developed. The patient died of cancer 12 months later. This case was considered to be Bellini's duct carcinoma as its features had poor prognosis and image findings infiltrating from medulla to cortex with the total enlargement of the kidney. To our knowledge there has been no case found like these atypical imaging findings.
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PMID:[A case of Bellini duct carcinoma with giant hydronephrosis]. 1557 21

Genetic, biochemical and physiological studies have demonstrated that the renin-angiotensin system (RAS) plays a fundamental role in kidney development. All of the components of the RAS are expressed in the metanephros. Mutations in the genes encoding components of the RAS in mice or pharmacological inhibition of RAS in animals or humans cause diverse congenital abnormalities of the kidney and lower urinary tract. The latter include renal vascular abnormalities, abnormal glomerulogenesis, renal papillary hypoplasia, hydronephrosis, aberrant UB budding, duplicated collecting system, and urinary concentrating defect. Thus, the actions of angiotensin (ANG) II during kidney development are pleiotropic both spatially and temporally. Whereas the role of ANG II in renovascular and glomerular development has received much attention, little is known about the potential role of ANG II and its receptors in the morphogenesis of the collecting system. In this review, we discuss recent genetic and functional evidence gathered from transgenic knockout mice and in vitro organ and cell culture implicating the RAS in the development of the ureteric bud and collecting ducts. A novel conceptual framework has emerged from this body of work which states that stroma-derived ANG II elicits activation of AT(1)/AT(2) receptors expressed on the ureteric bud to stimulate branching morphogenesis as well as collecting duct elongation and papillogenesis.
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PMID:Role of the renin-angiotensin system in the development of the ureteric bud and renal collecting system. 1594 83

Congenital progressive hydronephrosis (cph) is a spontaneous recessive mutation that causes severe hydronephrosis and obstructive nephropathy in affected mice. The mutation has been mapped to the distal end of mouse chromosome 15, but the mutated gene has not been found. Here, we describe the identification of a single base pair change in aquaporin-2 (Aqp2) in cph mutants through genetic linkage mapping. The C-T change led to the substitution of a Ser (S256) by a Leu in the cytoplasmic tail of the Aqp2 protein, preventing its phosphorylation at S256 and the subsequent accumulation of Aqp2 on the apical membrane of the collecting duct principal cells. The interference with normal trafficking of Aqp2 by this mutation resulted in a severe urine concentration defect. cph homozygotes demonstrated polydipsia and produced a copious amount of hypotonic urine. The urine concentration defect could not be corrected by [deamino-Cys1,D-Arg8]-vasopressin (DDAVP, a vasopressin analog), characteristic of nephrogenic diabetes insipidus. The nephrogenic diabetes insipidus symptoms and the absence of developmental defects in the pyeloureteral peristaltic machinery in the mutants before the onset of hydronephrosis suggest that the congenital obstructive nephropathy is most likely a result of the polyuria. This study has revealed the genetic basis for the classical cph mutation and has provided direct genetic evidence that S256 in Aqp2 is indispensable for the apical accumulation, but not the general glycosylation or membrane association, of Aqp2.
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PMID:Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. 1664 Oct 94

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

Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice. Forskolin and [desamino-Cys(1), D-Arg(8)]-vasopressin (DDAVP)-induced AQP2 exocytosis was impaired in VAMP8-null collecting duct cells. VAMP8 was revealed to colocalize with AQP2 on intracellular vesicles and to interact with the plasma membrane t-SNARE proteins syntaxin4 and syntaxin3, suggesting that VAMP8 mediates the regulated fusion of AQP2-positive vesicles with the plasma membrane.
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PMID:A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2. 1984 Oct 70


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