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Proximal Tubules (proximal + tubule)
Kinds of Proximal Tubules Terms modified by Proximal Tubules Selected AbstractsIntracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+ -ATPaseACTA PHYSIOLOGICA, Issue 2 2002F. R. IBARRA ABSTRACT The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on , -adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+ -adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+ -ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the , -adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+ -ATPase on the Ser23 residue. The level of PKC induced Na+,K+ -ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+ -ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+ -ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+ -ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+ -ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium-dependent protein phosphatase, calcineurin, increased the state of Na+,K+ -ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+ -ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis. [source] Tubular reabsorption and diabetes-induced glomerular hyperfiltrationACTA PHYSIOLOGICA, Issue 1 2010P. Persson Abstract Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A1 -receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand58, 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman's space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman's space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration. [source] The lateral intercellular space as osmotic coupling compartment in isotonic transportACTA PHYSIOLOGICA, Issue 1 2009E. H. Larsen Abstract Solute-coupled water transport and isotonic transport are basic functions of low- and high-resistance epithelia. These functions are studied with the epithelium bathed on the two sides with physiological saline of similar composition. Hence, at transepithelial equilibrium water enters the epithelial cells from both sides, and with the reflection coefficient of tight junction being larger than that of the interspace basement membrane, all of the water leaves the epithelium through the interspace basement membrane. The common design of transporting epithelia leads to the theory that an osmotic coupling of water absorption to ion flow is energized by lateral Na+/K+ pumps. We show that the theory accounts quantitatively for steady- and time dependent states of solute-coupled fluid uptake by toad skin epithelium. Our experimental results exclude definitively three alternative theories of epithelial solute,water coupling: stoichiometric coupling at the molecular level by transport proteins like SGLT1, electro-osmosis and a ,junctional fluid transfer mechanism'. Convection-diffusion out of the lateral space constitutes the fundamental problem of isotonic transport by making the emerging fluid hypertonic relative to the fluid in the lateral intercellular space. In the Na+ recirculation theory the ,surplus of solutes' is returned to the lateral space via the cells energized by the lateral Na+/K+ pumps. We show that this theory accounts quantitatively for isotonic and hypotonic transport at transepithelial osmotic equilibrium as observed in toad skin epithelium in vitro. Our conclusions are further developed for discussing their application to solute,solvent coupling in other vertebrate epithelia such as small intestine, proximal tubule of glomerular kidney and gallbladder. Evidence is discussed that the Na+ recirculation theory is not irreconcilable with the wide range of metabolic cost of Na+ transport observed in fluid-transporting epithelia. [source] Na+/H+ exchangers and the regulation of volumeACTA PHYSIOLOGICA, Issue 1-2 2006R. T. Alexander Abstract The regulation of volume is fundamental to life. There exist numerous conditions that can produce perturbations of cell volume. The cell has developed mechanisms to directly counteract these perturbations so as to maintain its physiological volume. Directed influx of the major extracellular cation, sodium, serves to counteract a decreased cell volume through the subsequent osmotically coupled movement of water to the intracellular space. This process, termed regulatory volume increase is often mediated by the ubiquitous sodium/hydrogen ion exchanger, NHE1. Similarly, the maintenance of intravascular volume is essential for the maintenance of blood pressure and consequently the proper perfusion of vital organs. Numerous mechanisms exist to counterbalance alterations in intravascular volume, not the least of which is the renal absorption of sodium filtered at the glomerulus. Two-thirds of filtered sodium and water are absorbed in the renal proximal tubule, a mechanism that intimately involves the apical sodium/hydrogen ion exchanger, NHE3. This isoform is fundamental to the maintenance and regulation of intravascular volume and blood pressure. In this article, the effects of cell volume on the activity of these different isoforms, NHE1 and NHE3, will be described and the consequences of their activity on intracellular and intravascular volume will be explored. [source] Time course of the renal functional response to partial nephrectomy: measurements in conscious ratsEXPERIMENTAL PHYSIOLOGY, Issue 1 2007R. M. Chamberlain Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of 99mTc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by ,50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at ,300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by ,30% after uninephrectomy and by ,120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient. [source] Fibroblast growth factor 23 reduces expression of type IIa Na+/Pi co-transporter by signaling through a receptor functionally distinct from the known FGFRs in opossum kidney cellsGENES TO CELLS, Issue 5 2005Xiaomei Yan Fibroblast growth factor (FGF) 23 is an important phosphaturic factor that inhibits inorganic phosphate (Pi) reabsorption from the renal proximal tubule. Its overproduction and proteolysis-resistant mutation such as R179Q cause tumor-induced osteomalacia and autosomal dominant hypophosphatemic rickets, respectively. To clarify the signaling mechanisms of FGF23 that mediate the reduction of Pi reabsorption, we inhibited the function of the known FGFRs in opossum kidney (OK-E) cells by expressing a dominant-negative (DN) form of FGFR. OK-E cells, which represent the renal proximal tubular cells, expressed all four known FGFRs. FGF23(R179Q) bound to and activated FGFR2, a prominent FGFR expressed in OK-E cells. The activated receptor transmitted a signal to increase the expression of type IIa Na+/Pi co-transporter and the Pi uptake. Expression of FGFR2(DN), which suppresses the major FGFR-mediated signal through the FRS2,-ERK pathway, reversed the function of FGF23(R179Q). When FGF23(R179Q) was applied to the basolateral side of polarized OK-E cells, regardless of the FGFR2(DN) expression, the apical Pi uptake decreased significantly. The apical application of FGF23(R179Q) in the polarized cells did not show such decrease but increase. The exogenously expressed FGFR2 was detectable only at the apical membrane. These results suggest that an FGF23 receptor, which is functionally distinct from the known FGFRs, is expressed at the basolateral membrane of OK-E cells. [source] Isolation, propagation and characterization of primary tubule cell culture from human kidney (Methods in Renal Research)NEPHROLOGY, Issue 2 2007WEIER QI SUMMARY: Proximal tubule cells (PTC) are the major cell type in the cortical tubulointerstitium. Because PTC play a central role in tubulointerstitial pathophysiology, it is essential to prepare pure PTC from kidney tissue to explore the mechanisms of tubulointerstitial pathology. The authors have successfully refined and characterized primary cultures of human PTC using Percoll density gradient centrifugation as a key PTC enrichment step. The cells obtained by this method retain morphological and functional properties of PTC and are minimally contaminated by other renal cells. In particular, the primary isolates have characteristics of epithelial cells with uniform polarized morphology, tight junction and well-formed apical microvilli. Cytokeratin is uniformly and strongly expressed in the isolates. Brush border enzyme activities and PTC transport properties are retained in the isolates. This method therefore provides an excellent in vitro model for the physiologic study of the human proximal tubule. [source] Low-grade renal cell carcinoma arising from the lower nephron: A case report with immunohistochemical, histochemical and ultrastructural studiesPATHOLOGY INTERNATIONAL, Issue 12 2001Masako Otani Most renal cell carcinomas (RCC) are composed of clear cells with sinusoid-like vasculatures and originate from the proximal tubule. On the other hand, collecting duct carcinoma (CDC) and chromophobe RCC are thought to originate from the lower nephron. In the present study, we present a case of unusual RCC. The patient was a 68-year-old Japanese woman who had developed general fatigue with hematuria. Computed tomography revealed a left renal tumor suggesting sarcoma. The resected tumor was located in the renal parenchyma, measuring 12 × 10 × 8 cm in size. Histologically, the tumor consisted principally of cuboidal cells forming parallel or radiating arrays, continuous with the spindle-shaped cells. Most parts of the tumor showed hemorrhagic necrosis. Immunohistochemically, tumor cells were positive for high molecular weight cytokeratins, vinculin, vimentin, CD15 and epithelial membrane antigen, and showed affinities with some kinds of lectins. N- and E-cadherins and , -catenin were diffusely positive in tumor cells. Nuclear positivity for Ki-67 and p53 protein were approximately 2.0 and 1.7%, respectively. Considering its morphological and histochemical natures, this tumor is considered to have originated from the lower nephron, which is unique for a tumor of low-grade malignancy. [source] Proteomic analysis of human proximal tubular cells exposed to high glucose concentrationsPROTEOMICS - CLINICAL APPLICATIONS, Issue 7-8 2008Eun-Jeong So Abstract Hyperglycemia is a major key factor in the pathogenesis of microvascular complications of diabetes, including diabetic nephropathy (DN). Most studies to date have focused on the glomerular abnormalities found in DN. However, nephromegaly in the early stages of diabetes and the correlation of tubulointerstitial pathology rather than glomerular pathology with declining renal function in DN suggests the involvement of the tubulointerstitium. The etiology of the tubulointerstitial pathology in DN, however, is not fully understood. In this study, to understand the DN pathways, we constructed an initial 2-DE reference map for primitively cultured human proximal tubule (HK-2) cell in the presence of 5,mM and 25,mM glucose, which correspond to blood glucose concentrations during the normal and hyperglycemia conditions, respectively. Differentially expressed HK-2 cell cellular proteins at the high glucose concentration were identified via ESI-Q-TOF MS/MS and confirmed by Western blotting; enolase 1 (up-regulated) and lactate dehydrogenase (down-regulated). The regulation of these proteins will help in understanding DN mechanism through the glycolysis metabolic pathways in high glucose stimulated HK-2 cells. [source] The regulation and function of phosphate in the human bodyBIOFACTORS, Issue 1-4 2004Eiji Takeda Abstract Inorganic phosphate (Pi) is required for cellular function and skeletal mineralization. Serum Pi level is maintained within a narrow range through a complex interplay between intestinal absorption, exchange with intracellular and bone storage pools, and renal tubular reabsorption. Pi is abundant in the diet, and intestinal absorption of Pi is efficient and minimally regulated. The kidney is a major regulator of Pi homeostasis and can increase or decrease its Pi reabsorptive capacity to accommodate Pi need. The crucial regulated step in Pi homeostasis is the transport of Pi across the renal proximal tubule. Type II sodium-dependent phosphate (Na/Pi) cotransporter (NPT2) is the major molecule in the renal proximal tubule and is regulated by hormones and nonhormonal factors. Recent studies of inherited and acquired hypophosphatemia which exhibit similar biochemical and clinical features, have led to the identification of novel genes, phosphate regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and fibroblast growth factor-23 (FGF-23), that play a role in the regulation of Pi homeostasis. The PHEX gene encodes an endopeptidase, predominantly expressed in bone and teeth but not in kidney. FGF-23 may be a substrate of this endopeptidase and inhibit renal Pi reabsorption. In a survey in the United States and in Japan, the amount of phosphorus from food is gradually increasing. It is thought that excess amounts of phosphorus intake for long periods are a strong factor in bone impairment and ageing. The restriction of phosphorus intake seems to be important under low calcium intake to keep QOL on high level. [source] An in vitro model of the kidney proximal tubuleBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2010Article first published online: 29 JUN 2010 No abstract is available for this article. [source] DIFFERENTIAL REGULATION OF ANGIOTENSIN II RECEPTORS DURING RENAL INJURY AND COMPENSATORY HYPERTROPHY IN THE RATCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2005Emma Joly SUMMARY 1.,The renin-angiotensin system may be involved in the compensatory adaptations occurring after the reduction of renal mass and during the consecutive changes leading to chronic renal failure. We therefore investigated the regulation of angiotensin II receptors in two models of renal hypertrophy in the rat: hypertrophy following uninephrectomy (UNx) or subtotal nephrectomy (STNx). The level of angiotensin type 1 (AT1A -R and AT1B -R) and type 2 (AT2 -R) receptor mRNA was quantified by competitive reverse transcription-polymerase chain reaction (RT-PCR) in specific renal zones and the intrarenal distribution of angiotensin II receptors was analysed by immunohistochemistry. 2.,In the UNx rats, AT1 -R mRNA expression was not modified in the cortex or in the inner stripe of the outer medulla of the residual kidney at any time after the surgery (1, 4 and 12 weeks). In contrast, AT1 -R mRNA expression was significantly reduced in these zones in STNx rats (,33% and ,40%, respectively). This downregulation was organ-specific, as AT1 -R mRNA levels were not modified in the liver. The proportions of AT1 -R subtype (AT1A and AT1B) mRNA were unchanged by UNx or STNx. Very low levels of AT2 -R mRNA were found in the cortex of all groups. Immunostaining revealed a similar localization of AT1 -R in mesangial cells, proximal tubule, basolateral membrane of thick ascending limb, in both models of hypertrophy. AT1 -R labelling was also detected in the apical membrane of intercalated cells of cortical collecting ducts. 3.,This differential mRNA expression of angiotensin II receptors during compensatory hypertrophy and renal injury suggests that the development of renal hypertrophy is independent of AT1 -R and AT2 -R gene expression levels. [source] Mechanisms of transjunctional transport of NaCl and water in proximal tubules of mammalian kidneysACTA PHYSIOLOGICA, Issue 1 2002F. KIILArticle first published online: 30 APR 200 ABSTRACT Tight junctions and the intercellular space of proximal tubules are not accessible to direct measurements of fluid composition and transport rates, but morphological and functional data permit analysis of diffusion and osmosis causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses through tight junctions along a chloride gradient, but against a sodium gradient. Calculation in terms of modified Nernst,Fick diffusion equation after eliminating electrical terms shows that transport rates (300,500 pmol min,1 mm,1 tubule length) and transepithelial voltage of +2 mV are in agreement with observations. Diffusion coefficients are Dtj=1500 ,m2 s,1 in the S1 segment, and Dtj=90,100 ,m2 s,1 in the S2 segment where apical intercellular NaCl concentration is 132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions with gap distance 6 Å are impermeable to mannitol (effective molecular radius 4 Å); reflection coefficients are ,=0.92 for NaHCO3 and ,=0.28 for NaCl, because of difference in anion size. The osmotic force is provided by a difference in effective transjunctional osmolality of 10 mOsm kg,1 in the S1 segment and 30 mOsm kg,1 in the S2 segment, where differences in transjunctional concentration contribute with 21 mOsm kg,1 for NaHCO3 and ,4 mOsm kg,1 for NaCl. Transjunctional difference of 30 mOsm kg,1 causes a volume flow of 2 nL min,1 mm,1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow and diffusive and convective transport of NaCl. In conclusion, transjunctional diffusion and osmosis along gradients generated by transcellular transport of other solutes account for all NaCl transport in proximal tubules. [source] Mechanisms of intercellular hypertonicity and isotonic fluid absorption in proximal tubules of mammalian kidneysACTA PHYSIOLOGICA, Issue 1 2002F. KIILArticle first published online: 30 APR 200 ABSTRACT The main purpose of this theoretical analysis (second of two articles) is to examine whether transjunctional diffusion of NaCl causes intercellular hypertonicity, which permits transcellular water transport across solute-impermeable lateral cell membranes until osmotic equilibration. In the S2 segment with tubular NaCl concentration 140 mM, the calculated apical intercellular NaCl concentration is c0 , 132 mM, which exceeds peritubular NaCl concentration by 12 mM or 22 mOsm kg,1. Variations in volume flow, junctional reflection coefficient (,NaCl=0.25,0.50), gap distance (g=6,8 Å), junctional depth (d=18,100 Å), intercellular diffusion coefficient (DLIS=500,1500 ,m2 s,1) and hypothetical active NaCl transport alter c0 only by a fraction of 1 mM. However, dilution and back-leakage of NaHCO3 lower apical intercellular hyperosmolality to ,18 mOsm kg,1. Water transport through solute-impermeable lateral cell membranes continues until intercellular and cellular osmolalities are equal. Transcellular and transjunctional volume flow are of similar magnitude (2 nL min,1 mm,1 tubule length) in the S2 segment. Thus, diffusion ensures isotonic absorption of NaCl. Two-thirds of NaHCO3 and other actively transported sodium salts are extruded into the last third of the exponentially widening intercellular space where the exposure time is only 0.9 s. Osmotic equilibration is dependent on aquaporins in the cell membranes. If permeability to water is low, transcellular water transport stops; tubular fluid becomes hypotonic; NaCl diffusion diminishes, but transjunctional water transport remains unaltered as long as transcellular transport of NaHCO3 and other solutes provides the osmotic force. [source] The ameliorative effect of cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2007B.H. Ali Abstract Pathogenesis of nephrotoxicity of the synthetic anticancer drug cisplatin (CP) involves generation of reactive oxygen species and free radicals in the kidney cortex, and cysteine prodrug l -2-oxothiazolidine-4-carboxylic acid (OTC) has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of OTC on CP nephrotoxicity in rats. OTC was given at an oral dose of 150 mg/kg/day for 7 days. On day 7, some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg. Rats were killed, blood and urine samples were collected, and the kidneys were removed 6 days after CP treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex, and by urinalyses. CP significantly increased the concentrations of urea and creatinine (P < 0.05) by about 128% and 170% respectively. CP treatment reduced cortical GSH concentration by about 34% (P < 0.05), and the activity of SOD by about 28% (P < 0.05). CP treatment significantly increased urine volume and N -acetyl- , - d -glucosaminidase (NAG) activity, and significantly decreased osmolality and protein concentrations. OTC significantly mitigated all these effects. Sections from saline- and OTC-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This appeared to be lessened when CP was given simultaneously with OTC. The concentration of CP in the cortical tissues was not significantly altered by OTC treatment. The results suggested that OTC had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, OTC may potentially be useful as a nephroprotective agent. [source] The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 casesHISTOPATHOLOGY, Issue 5 2004C-C Pan Aims:, To demonstrate the diagnostic utility of MOC31, BerEP4, renal cell carcinoma marker (RCC Ma) and CD10 in the classification of RCC and renal oncocytoma, based upon a comprehensive immunohistochemical analysis. Methods and results:, Immunohistochemistry was performed on 328 samples consisting of 256 clear cell/conventional, 27 papillary, 28 chromophobe, five collecting duct, five unclassified RCCs and seven renal oncocytomas using antibodies MOC31, BerEP4 and antibodies against cytokeratins (KL-1, CAM5.2, 34,E12, cytokeratin 7), RCC Ma, epithelial membrane antigen, E-cadherin, CD10, CD15 and vimentin. Multivariate analysis showed that MOC31, BerEP4, RCC Ma and CD10 have discriminatory value. MOC31 and BerEP4 chiefly labelled distal tubules of normal kidney while RCC Ma and CD10 labelled the proximal tubules. Twenty-three chromophobe RCCs (82%) were reactive for MOC31, while only four clear cell RCCs and three papillary RCCs were positive for this marker. Clear cell RCCs were characterized by a high positive rate for CD10 (82%) and a low positive rate for BerEP4 (27%). Papillary RCCs frequently coexpressed RCC Ma and BerEP4 (51%). All renal oncocytomas were negative for MOC31 and CD10. Conclusions:, MOC31 has diagnostic merit in discerning chromophobe RCC. The CD10+/BerEP4, profile and RCC Ma+/BerEP4+ profile achieve moderate sensitivity and good specificity for clear cell RCC and papillary RCC, respectively. The non-reactivity for both MOC31 and CD10 is helpful in distinguishing renal oncocytoma from RCC. When properly selected, antibodies have immunohistochemical diagnostic utility for the classification of renal cortical epithelial tumours. [source] Regional DNA hypermethylation and DNA methyltransferase (DNMT) 1 protein overexpression in both renal tumors and corresponding nontumorous renal tissuesINTERNATIONAL JOURNAL OF CANCER, Issue 2 2006Eri Arai Abstract To evaluate the significance of altered DNA methylation during renal tumorigenesis, tumorous tissues (T) and corresponding nontumorous renal tissues (N) from 94 patients with renal tumors, and normal renal tissues (C) from 16 patients without renal tumors were investigated. DNA methylation status on CpG islands of the p16, human MutL homologue 1 (hMLH1), von-Hippel Lindau (VHL) and thrombospondin-1 (THBS-1) genes and the methylated in tumor (MINT) -1, -2, -12, -25 and -31 clones and DNA methyltransferase (DNMT) 1 expression were examined by bisulfite modification and immunohistochemistry, respectively. The average number of methylated CpG islands was significantly higher in N than in C, and was even higher in T. The average number of methylated CpG islands in N was significantly correlated with a higher histological grade of corresponding conventional renal cell carcinomas (RCCs). The average number of methylated CpG islands in RCCs was significantly correlated with macroscopic configuration with extranodular or multinodular growth, higher histological grade, infiltrating growth pattern and vascular involvement. The recurrence-free survival rate of patients with RCCs showing accumulation of DNA methylation was significantly lower than that of patients not showing this feature. The incidence of nuclear immunoreactivity for DNMT1 tended to be higher in proximal tubules from N than in those from C, and was significantly higher in RCCs. From the viewpoint of altered DNA methylation, N is at the precancerous stage, and N showing accumulation of DNA methylation may generate more malignant RCCs. Regional DNA hypermethylation may be associated with renal tumorigenesis from a precancerous condition to malignant progression and become a predictor of patient prognosis. © 2006 Wiley-Liss, Inc. [source] Curcuma Aromatica Inhibits Diabetic Nephropathy in the RatJOURNAL OF FOOD SCIENCE, Issue 9 2006Ji-Young Hong ABSTRACT:, To test the possible involvement of reactive oxygen species (ROS) in the etiology of diabetic complications and therapeutic potential of antioxidant biofactors, we studied the effects of Curcuma aromatica (C. aromatica) on the pathologic events in streptozotocin-treated diabetic rats. Administration of streptozotocin (100 mg/kg, i.p.) increased plasma levels of glucose, triglyceride, cholesterol, urea nitrogen (BUN), creatinine, and lipid peroxidation products but decreased plasma albumin levels and suppressed the growth of animals. Histological examination revealed a marked injury in renal glomeruli and proximal tubules with concomitant occurrence of 8-hydroxy-2,-deoxyguanosine (8-OHdG) and mitochondrial 4-hydroxy-2-nonenal (4-HNE). Urinary excretion of 8-OHdG was also increased in streptozotocin-treated animals. Administration of streptozotocin decreased the mitochondrial localization of both Cu/Zn-superoxide dismutase (SOD) and cytochrome C in the kidney without affecting the localization of Mn-SOD. When animals were given 1.5%C. aromatica- containing diet for 1 wk before and 8 wk after administration of streptozotocin, all the events induced by streptozotocin except for hyperglycemia decreased markedly. Thus, C. aromatica may have therapeutic potential for the prevention of hyperglycemia-associated diabetic complications. [source] Bioimaging TOF-SIMS of tissues by gold ion bombardment of a silver-coated thin sectionMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2004Håkan Nygren Abstract The imaging time-of-flight secondary-ion-mass-spectrometry (TOF-SIMS) method was utilized to address the problem of cholesterol localization in rat tissues. Rat kidneys were fixed, cryoprotected by sucrose, frozen, sectioned by cryoultramicrotomy, and dried at room temperature. The samples were either covered with a thin silver layer or analyzed uncovered in an imaging TOF-SIMS instrument equipped with an Au -source. The yield of desorbed secondary ions for some species was up to 600-fold higher after silver coating of the samples. Reference samples of cholesterol were silver-coated and analyzed by TOF-SIMS to define significant peaks, specific for cholesterol. Such peaks were found at m/z = 386 (C27H46O+), m/z = 493 (C27H46O107Ag+), m/z = 495 (C27H46O109Ag+), m/z = 879 (C54H92O2107Ag+), and m/z = 881 (C54H92O2109Ag+). The silver-cationized cholesterol (493 , m/z , 495) signal was localized by imaging TOF-SIMS in the kidney sections and showed a high cholesterol content in the kidney glomeruli. A more diffuse distribution of cholesterol was also found over areas representing the cytoplasm or plasma membrane of the epithelial cells in the proximal tubules of rat kidney. Microsc. Res. Tech. 65:282,286, 2004. © 2005 Wiley-Liss, Inc. [source] Aldosterone induces collagen synthesis via activation of extracellular signal-regulated kinase 1 and 2 in renal proximal tubulesNEPHROLOGY, Issue 8 2008GUOSHUANG XU SUMMARY: Aim: Aldosterone plays a crucial role in renal fibrosis by inducing mesangial cell proliferation and promoting collagen synthesis in renal fibroblasts. However, renal proximal tubule involvement in aldosterone-induced collagen synthesis has not yet been identified. The aim of this study was to examine the potential role of aldosterone in collagen expression and its possible mineralocorticoid receptor (MR)-dependent pathway, mediated by activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal proximal tubular epithelial (HKC) cells. Methods: After HKC cells were stimulated by aldosterone with different concentrations for various time and periods, the gene expression and protein synthesis of collagen I, II, III and IV were measured by real-time polymerase chain reaction and western blot, respectively. ERK1/2 activation, ,-smooth muscle actin (,-SMA), and E-cadherin were also detected by western blot. Results: Aldosterone can increase ERK1/2 phosphorylation of human renal proximal tubular epithelial cells in a time- and dose-dependent manner. Although aldosterone had no effect on collagen I and II expression, it increased expression of ,-SMA and collagen III and IV and decreased that of E-cadherin in HKC cells after 48 h. These effects could be prevented by a ERK pathway inhibitor, U0126, or by a selective MR antagonist, spironolactone. Conclusion: The results suggest that aldosterone plays a pivotal role in tubulointerstitial fibrosis by promoting tubular epithelial,mesenchymal transition and collagen synthesis in proximal tubular cells. The process is MR-dependent, and mediated by ERK1/2 mitogen-activated protein kinase pathway. [source] Mixed epithelial and stromal tumor of the kidney in a 12-year-old girlPATHOLOGY INTERNATIONAL, Issue 10 2005Noboru Hara Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare kidney neoplasm that almost exclusively occurs in perimenopausal women, and long-term estrogen replacement is relevant to its pathogenesis. Herein is described an atypical case of MESTK uncovered in a 12-year-old premenarcheal girl without a history of prior estrogen use. On surgical specimen it was found that the well-circumscribed tumor measuring 14 cm arose from the lower pole of the right kidney, showing solid and fibrous-cystic areas. Microscopically, it was composed both of epithelial structures similar to renal tubules and stroma comprising non-specific spindle cells. Some intratumoral tubules showed affinities to distal-nephron-specific lectins, and those immunoreactive for proximal-tubule-specific CD15 were also present. In addition, primitive ductal structures were reactive both for CD15 and lectins, but immature epithelial elements typical of nephroblastoma were absent. Spindle cells were positive for actin, desmin and vimentin, and expressed progesterone and estrogen receptors. The tumor was comparable with MESTK, although some epithelia were associated with the immunophenotype of proximal tubules. The patient was free of disease postoperatively for 40 months. In the present case, remnants of the primitive periductal mesenchyme might be promoted to neoplastic cells by a sex-steroid surge during puberty. [source] Establishment and characterization of three new rat renal cell carcinoma cell lines from N -ethyl- N -hydroxyethylnitrosamine-induced basophilic cell tumorsPATHOLOGY INTERNATIONAL, Issue 2 2001Reiko Tokuzen Three new rat cell lines (designated as BP13, BP30 and BP36B), derived from rat basophilic-type renal cell carcinomas induced with N -ethyl- N -hydroxyethylnitrosamine, were established and characterized. Passaged up to 100 times in vitro for 3 years, each cell line forms epithelial monolayers with cell cycles for BP13, BP30 and BP36B of 29, 21 and 17 h, respectively. Positive glucose-6-phosphate dehydrogenase (G6PD) and ,-glutamyltransferase (,-GT) activity in their cytoplasm, but negative succinate dehydrogenase (SD) and slightly positive carbonic anhydrase type II (CA) localization indicates an origin from proximal tubules. Ultrastructural examination showed the presence of variable numbers of mitochondria and many microvilli and intracellular junctions on the plasma membrane. BP13 and BP30 were found to be tetraploid and BP36B diploid. BP13 has one marker chromosome 15p+, and BP36B an isochromosome of 1q. Anchorage-independent growth and tumorigenicity in immunosuppressed nude mice of BP13 and BP36B, but not BP30, proved their neoplastic nature. These three cell lines should provide useful tools for studying the biological characteristics of renal cell tumors. [source] Renal carcinogenesis induced by ferric nitrilotriacetate in mice, and protection from it by Brazilian propolis and Artepillin CPATHOLOGY INTERNATIONAL, Issue 9 2000Tetsuo Kimoto The protective effect of Brazilian propolis and its extract Artepillin C against ferric nitrilotriacetate (Fe-NTA)-induced renal lipid peroxidation and carcinogenesis was studied in male ddY mice. Fe-NTA-induced renal lipid peroxidation leads to a high incidence of renal cell carcinoma (RCC) in mice. Administration of propolis by gastric intubation 2 h before or Artepillin C at either the same time, 2 h, or 5 h before the intraperitoneal injection of Fe-NTA (7 mg Fe/kg) effectively inhibited renal lipid peroxidation. This was evaluated from the measurement of renal thiobarbituric acid-reactive substances (TBARS) or histochemical findings of 4-hydroxy-2-nonenal (4-HNE)-modified proteins and 8-hydroxy-2, -deoxyguanosine (8-OHdG). Repeated injection of Fe-NTA (10 mg Fe/kg per day, twice a week for a total of 16 times in 8 weeks) caused subacute nephrotoxicity as revealed by necrosis and pleomorphic large nuclear cells in the renal proximal tubules, and gave rise to RCC 12 months later. A protective effect from carcinogenicity was observed in mice given propolis or Artepillin C. Furthermore, the mice given Fe-NTA only developed multiple cysts composed of precancerous lesions with multilayered and proliferating large atypical cells. Mice treated with propolis and Artepillin C also had cysts, but these were dilated and composed of flat cells. These results suggest that propolis and Artepillin C prevent oxidative renal damage and the carcinogenesis induced by Fe-NTA in mice. [source] Comparative immunohistochemical analysis of developing kidneys, nephroblastomas and related tumors: Considerations on their histogenesisPATHOLOGY INTERNATIONAL, Issue 6 2000Fumiko Satoh Immunoperoxidase analysis was performed to evaluate the phenotypic expression of eight renal differentiation antigens in five nephroblastomas, one clear cell sarcoma of the kidney (CCSK), one rhabdoid tumor of the kidney (RTK), and four related tumors. A total of 19 fetal and pediatric kidneys, including two 6th -week mesonephric tissues, were comparatively studied. All the specimens were fixed in formalin and embedded in paraffin. Neural cell adhesion molecule (NCAM), a marker of the nephrogenic zone of the developing kidney, was consistently expressed in the epithelial and blastematous components of nephroblastomas of the common type. The epithelial components also commonly expressed NK1 and Leu 7 (CD57), and the findings may reflect that both were positive in immature proximal tubules directly differentiating from the NCAM-positive immature fetal tubuloglomerular buds. In two cases, the epithelial component was immunoreactive for CD10 and WT1 gene product (WT1-GP). Leu M1, epithelial membrane antigen and CA15,3 were only focally expressed in nephroblastomas. Rhabdomyoblasts in the stroma were positive for WT1-GP. CCSK was featured by the expression of NCAM and CD10. In RTK, focal epithelial differentiation was discerned, with focal positivity of WT1-GP and negativity of NCAM. In congenital mesoblastic nephroma, the stromal spindle cells were strongly immunoreactive for WT1-GP, while WT1-GP was not expressed in solitary multilocular cyst of the kidney. Pancortical nephroblastomatosis was featured by the diffuse subcapsular reappearance of immature metanephric tissue. Nephroblastomas and related conditions thus offer an adequate model for studying human nephrogenesis. [source] Tubular kidney injury molecule-1 (KIM-1) in human renal disease,THE JOURNAL OF PATHOLOGY, Issue 2 2007MM van Timmeren Abstract KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with urinary KIM-1 (uKIM-1) is unknown. In biopsies from various renal diseases (n = 102) and controls (n = 7), the fraction of KIM-1 positive tubules and different renal damage parameters were scored. Double labelling was performed for KIM-1 with macrophages (MØ), ,-smooth muscle actin (,-SMA), proximal (aquaporin-1) and distal (E-cadherin) tubular markers and a dedifferentiation marker (vimentin). uKIM-1 at the time of biopsy (n = 53) was measured by ELISA. Renal KIM-1 was significantly increased in all diseases versus controls (p < 0.05), except minimal change. KIM-1 was primarily expressed at the luminal side of dedifferentiated proximal tubules, in areas with fibrosis (,-SMA) and inflammation (MØ). Independent of the disease, renal KIM-1 correlated positively with renal damage, negatively with renal function, but not with proteinuria. uKIM-1 was increased in renal patients versus controls (p < 0.001), including minimal change, and correlated positively with tissue KIM-1 and MØ, negatively with renal function, but not with proteinuria. In conclusion, KIM-1 is upregulated in renal disease and is associated with renal fibrosis and inflammation. uKIM-1 is also associated with inflammation and renal function, and reflects tissue KIM-1, indicating that it can be used as a non-invasive biomarker in renal disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Benefits and risks of furosemide in acute kidney injuryANAESTHESIA, Issue 3 2010K. M. Ho Summary Furosemide, a potent loop diuretic, is frequently used in different stages of acute kidney injury, but its clinical roles remain uncertain. This review summarises the pharmacology of furosemide, its potential uses and side effects, and the evidence of its efficacy. Furosemide is actively secreted by the proximal tubules into the urine before reaching its site of action at the ascending limb of loop of Henle. It is the urinary concentrations of furosemide that determine its diuretic effect. The severity of acute kidney injury has a significant effect on the diuretic response to furosemide; a good ,urinary response' may be considered as a ,proxy' for having some residual renal function. The current evidence does not suggest that furosemide can reduce mortality in patients with acute kidney injury. In patients with acute lung injury without haemodynamic instability, furosemide may be useful in achieving fluid balance to facilitate mechanical ventilation according to the lung-protective ventilation strategy. [source] Expression of Hepatocyte Nuclear Factor 4, in Developing MiceANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2009T. Kanazawa Summary Hepatocyte nuclear factor (HNF) 4,, a transcription factor of the nuclear hormone receptor family, is generally expressed in some endoderm-derived epithelial tissues such as hepatocytes. In mice, an alternative promoter referred to as the P2 promoter is located upstream from the P1 promoter, resulting in the transcription of at least nine isoforms. In this study, we investigated the expression of Hnf4, in adult and embryonic mouse tissues, paying special attention to the developing metanephros by using immunohistochemistry and reverse transcriptase-polymerase chain reaction for the detection of P1 and/or P2 promoter-derived products. In adult mouse tissues, the kidney was the only organ expressing Hnf4, controlled only by the P1 promoter, and HNF4, was detected in the nuclei of epithelial cells in the proximal tubules, but not in other components of the nephron. In the metanephros, HNF4, was detected first at the epithelial cell nuclei in part of the comma-shaped body, distributed widely throughout the developing nephron and finally restricted to the proximal tubules. Interestingly, it was noted that Hnf4, mRNAs from stomach, pancreas and kidney tissues in embryonic periods were transcribed by both promoters. Immunohistochemistry for HNF4, and HNF1, revealed that both factors involved the same network of transcription factors, giving the impression that HNF4, was upstream of HNF1,. [source] Immunolocalization of Na+, K+ -ATPase-rich cells in the gill and urinary system of Persian sturgeon, Acipenser persicus, fryAQUACULTURE RESEARCH, Issue 3 2009Saber Khodabandeh Abstract Localization of Na+, K+ -ATPase-rich cells in the gill and urinary system of Acipenser persicus fry was performed through immunofluorescence light microscopy using a mouse monoclonal antibody IgG,5 raised against the ,-subunit of chicken Na+, K+ -ATPase. Different types of epithelia were clearly identified in the gill epithelium: epithelia of branchial arch, interbranchial septum, filament and lamellar epithelium. The Na+, K+ -ATPase-rich cells were found in the epithelia of branchial arch, interbranchial septum, filament, interlamellar region and also in the lamellae. Histologically, the urinary system is divided into head kidney, trunk kidney and short caudal kidney. The head kidney is composed of the pronephric tubules and the haemopoietic tissues, while the trunk kidney is composed of a large number of glomeruli and convoluted nephrons. Each nephron consisted of a large glomerulus and tubules (neck, proximal, distal and collecting tubules) which connected to ureters. Posteriorly, ureters extended and joined together to form a small urinary bladder. In the urinary system, no specific fluorescence staining was observed in the glomerulus, neck segment and proximal tubules. The distal tubule cells and collecting tubule cells showed a strong immunostaining of Na+, K+ -ATPase. Epithelia of ureters and urinary bladder also showed several isolated immunofluorescent cells. Immunofluorescent cells were rich in Na+, K+ -ATPase enzyme which is very important for osmoregulation. [source] Renal glutathione transport: Identification of carriers, physiological functions, and controversiesBIOFACTORS, Issue 6 2009Lawrence H. Lash Abstract Glutathione (GSH) is an endogenous tripeptide composed of the amino acids L -glutamate, L -cysteine, and glycine. It is found in virtually all aerobic cells and plays critical roles in maintenance of cellular redox homeostasis and drug metabolism. An important component of its regulation is transport across biological membranes. Because GSH is a charged, hydrophilic molecule, transport occurs via catalysis by specific carrier proteins rather than by simple diffusion. Although it has been clearly understood that efflux of GSH across membranes such as the canalicular and sinusoidal plasma membranes in hepatocytes and the brush-border plasma membrane in renal proximal tubules is a key step in GSH turnover and interorgan metabolism, the existence and physiological functions of uptake of GSH across various epithelial plasma membranes has been subject to some debate. Besides transport across plasma membranes, GSH transport across intracellular membranes, most notably the mitochondrial inner membrane, has received some attention in recent years because of the importance of mitochondrial redox status and the mitochondrial GSH pool in cellular physiology and pathology. This commentary will focus on renal transport processes for GSH and will discuss some of the controversies that have existed and still seem to exist in the literature, specifically regarding uptake of intact GSH by basolateral membranes of renal proximal tubular cells and uptake of intact GSH by the mitochondrial inner membrane. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] Altered expression of aquaporin-2 in human explants with chronic renal allograft dysfunctionBJU INTERNATIONAL, Issue 7 2005Kossen M.T. Ho OBJECTIVE To investigate the distribution of aquaporins, a recently discovered family of transmembrane water channels, in human renal explants, with specific reference to chronic renal allograft dysfunction (CRAD). MATERIALS AND METHODS Immunohistochemistry for aquaporin-1 and -2 was used in 11 explants, of which five had clinically and histologically confirmed CRAD. Controls were taken from the six explants unaffected by CRAD and from histologically normal areas of six kidneys excised for renal tumours. RESULTS In the renal tumour control group, aquaporin-1 immunoreactivity was detected in the glomerular endothelium, Bowman's capsule, the proximal convoluted tubules and the thin limb of the loop of Henle, whereas immunoreactivity for aquaporin-2 was detected in the collecting ducts only. Of the explants without CRAD, where architecture was preserved, immunoreactivity for aquaporin-1 and -2 was the same as in the renal tumour controls. In the two explants with no CRAD and loss of collecting ducts, there was no aquaporin-2 immunoreactivity. In five explants with CRAD, immunoreactivity for aquaporin-2 was decreased or absent from the medulla to the cortex. The apparent decreased immunoreactivity of aquaporin-1 in this group was secondary to a decrease in the number of viable proximal tubules. CONCLUSION There was less aquaporin-2 immunoreactivity in human renal explants diagnosed with CRAD, starting from the medullary region. In explants with no CRAD and viable collecting ducts, or in normal controls, aquaporin-2 immunoreactivity remained unchanged. Aquaporins might be useful as markers for CRAD. [source] | ||||||||||||||||||||||||||||