Experimental nephrology最新文献

{"title":"Phenotypic modifications of human mesangial cells by extracellular matrix: the importance of matrix in the contractile response to reactive oxygen species.","authors":"M C Iglesias-De La Cruz,&nbsp;M P Ruiz-Torres,&nbsp;F J De Lucio-Cazaña,&nbsp;M Rodríguez-Puyol,&nbsp;D Rodríguez-Puyol","doi":"10.1159/000020655","DOIUrl":"https://doi.org/10.1159/000020655","url":null,"abstract":"<p><p>The progression of chronic renal diseases is characterized by the accumulation of extracellular matrix proteins in the glomerulus. The present experiments were designed to analyze the effect of hydrogen peroxide on the contractile and proliferative phenotypes of human mesangial cells grown on different culture substrates: plastic, collagen type I, and collagen type IV. Contraction was analyzed by measuring planar cell surface area and myosin light chain phosphorylation, whereas proliferation was studied by [(3)H]thymidine incorporation. No changes were detected in the proliferation rate of human mesangial cells grown on different culture substrates, neither under basal conditions nor in the presence of fetal calf serum or H(2)O(2). Cells grown on plastic or collagen did not contract in the presence of H(2)O(2), but cells grown on collagen I elicited a significant contraction with H(2)O(2). Platelet-activating factor induced contraction of human mesangial cells on the three culture substrates. The different contractile responses observed were not due to different degradation rates of H(2)O(2). The present experiments support the importance of extracellular matrix in the response to exogenous stimuli and point to the possibility that patients with changes in the mesangial matrix as a result of chronic renal diseases may have an increased susceptibility to the pathological actions of reactive oxygen species.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 2","pages":"97-103"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21581680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic plasticity and terminal differentiation of the intercalated cell: the hensin pathway.","authors":"Q Al-Awqati,&nbsp;S Vijayakumar,&nbsp;J Takito,&nbsp;C Hikita,&nbsp;L Yan,&nbsp;T Wiederholt","doi":"10.1159/000020650","DOIUrl":"https://doi.org/10.1159/000020650","url":null,"abstract":"The intercalated cell of the collecting tubule exists in a spectrum of types. The alpha form secretes acid by an apical H+ ATPase and a basolateral Cl:HCO3 exchanger which is an alternatively spliced form of the red cell band 3 (kAE1), while the beta form secretes HCO3 by having these transporters on the reverse membranes. In a clonal cell line of the beta form we found that seeding density causes this conversion. A new protein, termed hensin, was deposited in the extracellular matrix of high-density cells which on purification reversed the polarity of the transporters. Hensin also induced the expression of the microvillar protein, villin, and caused the appearance of the apical terminal web proteins, cytokeratin 19 and actin, all of which led to the development of an exuberant microvillar structure. In addition, hensin caused the beta cells to assume a columnar shape. All of these studies demonstrate that the conversion of polarity in the intercalated cell, at least in vitro, represents terminal differentiation and that hensin is the first protein in a new pathway that mediates this process. Hensin, DMBT1, CRP-ductin, and ebnerin are alternately spliced products from a single gene located on human chromosome 10q25–26, a region often deleted in several cancers, especially malignant gliomas. Hensin is expressed in many epithelial cell types, and it is possible that it plays a similarly important role in the differentiation of these epithelia as well.","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 2","pages":"66-71"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin.","authors":"S Holt,&nbsp;K Moore","doi":"10.1159/000020651","DOIUrl":"https://doi.org/10.1159/000020651","url":null,"abstract":"<p><p>Rhabdomyolysis causes renal dysfunction associated with renal vasoconstriction, tubular toxicity and luminal obstruction. There is now accumulating evidence that renal injury, caused by lipid peroxidation, is important in the pathogenesis of renal failure. The proposed central role of free iron in this process is examined. Current data have shown that the heme center of myoglobin can initiate lipid peroxidation and renal injury without invoking release of free iron, and this process is due to redox cycling of the heme group from ferrous to ferric and to ferryl oxidation states. Alkaline conditions prevent myoglobin-induced lipid peroxidation by stabilizing the reactive ferryl myoglobin complex. This review explores the evidence for each of these mechanisms.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 2","pages":"72-6"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous inhibition of renal phospholipase A(2) and glutathione synthesis by manoalide and DL-buthionine sulfoximine induces acute tubular dysfunction in rats.","authors":"A Soejima,&nbsp;S Ishizuka,&nbsp;N Miyake,&nbsp;K Fukuoka,&nbsp;M Suzuki,&nbsp;Y Kamiya,&nbsp;T Nagasawa","doi":"10.1159/000020653","DOIUrl":"https://doi.org/10.1159/000020653","url":null,"abstract":"We have previously demonstrated that gentamicin-induced acute renal failure is mediated by the consumption of renal glutathione (GSH) and accumulation of oxidized phospholipids in tubular epithelial cells as a result of inhibition of phospholipase A2 (PLA2) activity. Based on these results, we tested the hypothesis that the simultaneous inhibition of PLA2 and GSH synthesis induces acute renal failure similar in characteristics to gentamicin-induced acute renal failure. Male Sprague-Dawley rats kept under standard laboratory conditions were administered 3 mmol/kg of DL-buthionine sulfoximine (BSO; γ-glutamylcysteine synthetase inhibitor) and 30 μg/kg of manoalide (PLA2 inhibitor), following which significant elevations in serum creatinine and urinary lysosomal enzyme levels (elevation of N-acetyl-β-D-glucosaminidase activity) were observed. The renal tissue GSH content was reduced in the group that received both BSO and manoalide as compared with the group that received manoalide alone. The renal tissue GSH content was also reduced in the group that received BSO alone. The renal tissue concentration of 2-thiobarbituric-acid-reactive substances increased rapidly, followed by an increase in renal tissue total phospholipid concentration in the group that received both BSO and manoalide. In contrast, the activity of PLA2 in renal tissue decreased in the group that received both BSO and manoalide as compared with the groups that received BSO alone or physiological saline. In conclusion, concomitant administration of BSO and manoalide induces renal tubular damage and acute renal failure in rats, similar in characteristics to gentamicin-induced nephrotoxicity, whereas administration of BSO or manoalide alone did not. These results suggest that both inhibition of PLA2 and GSH depletion are necessary for the induction of acute renal failure.","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 2","pages":"84-90"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020653","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21580573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium restriction decreases AP-1 activation after nephron reduction in the rat: role in the progression of renal lesions.","authors":"F Terzi,&nbsp;M Burtin,&nbsp;M Hekmati,&nbsp;C Jouanneau,&nbsp;H Beaufils,&nbsp;G Friedlander","doi":"10.1159/000020656","DOIUrl":"https://doi.org/10.1159/000020656","url":null,"abstract":"<p><p>Renal hyperplasia and hypertrophy are early events after nephron reduction which precede progressive destruction of the remnant kidney. Restriction of dietary sodium content was shown to reduce renal lesions following nephron reduction. AP-1 is a transcription factor, resulting from heterodimerization of fos and jun proteins, which mediates the effects of mitogenic growth factors. To elucidate the role of AP-1 in growth processes involved in renal deterioration, we evaluated whether restriction of dietary sodium content (0.25 vs. 0.50% sodium w/w) affected AP-1-DNA binding and hyperplasia in the remnant kidney after nephron reduction (70% nephrectomy). Cell proliferation, evaluated by PCNA immunostaining, increased progressively from day 7 to day 60 in glomeruli, proximal and distal tubules and loops of Henle of nephrectomized (Nx) rats compared to control sham-operated (C) animals. AP-1-DNA binding activity increased 7 and 14 days after surgery, but it was reduced below C values at day 60. c-fos and c-jun expression were also reduced in Nx rats at day 60. Sodium restriction significantly reduced the number of PCNA-stained cells in glomeruli and tubules at days 14 and 60, but not at day 7, whereas it decreased AP-1 activation at all times of the study. This effect was associated to a marked reduction of renal lesions in Nx rats. In conclusion, we showed that, after nephron reduction, the beneficial effect of sodium restriction was associated with a reduction of hyperplasia and AP-1 activation, but that the latter did not parallel delayed cell proliferation rate in remaining nephrons. Thus, we propose that different transduction pathways are involved in cell proliferation after nephron reduction, according to the time of evolution of renal lesions.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 2","pages":"104-14"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21581683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caldesmon isoform associated with phenotypic modulation of mesangial cells.","authors":"K Okamoto,&nbsp;N Kashihara,&nbsp;Y Yamasaki,&nbsp;K Kanao,&nbsp;Y Maeshima,&nbsp;T Sekikawa,&nbsp;H Sugiyama,&nbsp;T Murakami,&nbsp;H Makino","doi":"10.1159/000020644","DOIUrl":"https://doi.org/10.1159/000020644","url":null,"abstract":"<p><p>Caldesmon (CaD) is a major calmodulin- and actin-binding protein distributed in smooth muscle cells (SMC) and nonmuscle cells. There are at least two high-molecular-weight CaD (h-CaD) isoforms and four low-molecular-weight CaD (l-CaD) isoforms produced by alternative splicing. Isoformal interconversion is associated with phenotypic modulations of vascular SMC. We investigated the CaD isoform in human and rat glomerular mesangial cells (MC) to characterize the phenotypic changes of MC involved in glomerular diseases. A Western blot analysis and reverse-transcription analysis using exon-specific primers revealed that one l-CaD isoform lacking exons 1, 3b and 4 was predominantly expressed in human cultured MC. The expression of this isoform was markedly enhanced in anti-Thy1.1 nephritis rats and streptozotocin-induced diabetic rats, while little expression was observed in the normal glomerulus. Isoformal interconversion did not occur during the phenotypic changes of MC. These data suggested that the activated MC resembled dedifferentiated SMC in terms of the CaD expression pattern, and that CaD is a useful marker of the phenotypic modulations of MC.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 1","pages":"20-7"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020644","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21499942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of endonucleases in renal tubular epithelial cell injury.","authors":"N Ueda,&nbsp;S V Shah","doi":"10.1159/000020642","DOIUrl":"https://doi.org/10.1159/000020642","url":null,"abstract":"<p><p>The study of cell death has emerged as an important and exciting area of research in cell biology. Although two kinds of cell death, apoptosis and necrosis, are recognized, one of the major advances in our understanding of cell death has been the recognition that the pathways traditionally associated with apoptosis may be very critical in the form of cell injury associated with necrosis. Renal tubular epithelial cell injury from ischemia or toxins has generally been regarded as a result of a necrotic form of cell death. We briefly describe recent evidence indicating apoptotic mechanisms including endonuclease activation in renal tubular injury and some mediators (oxidants, caspases and ceramide) which regulate this process. The pathway that is followed by the cell is dependent on both the nature and severity of insults, and it is likely that the cascades that lead to the apoptotic or necrotic mode of cell death are activated almost simultaneously and may share some common pathways.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 1","pages":"8-13"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21499996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective induction of MCP-1 in human mesangial cells by the IL-6/sIL-6R complex.","authors":"I Coletta,&nbsp;L Soldo,&nbsp;N Polentarutti,&nbsp;F Mancini,&nbsp;A Guglielmotti,&nbsp;M Pinza,&nbsp;A Mantovani,&nbsp;C Milanese","doi":"10.1159/000059327","DOIUrl":"https://doi.org/10.1159/000059327","url":null,"abstract":"<p><p>Interleukin (IL) 6, an autocrine growth factor for mesangial cells, and chemokines, which are released from activated mesangial cells and induce leukocyte infiltration, play a critical role in the progression of immune system mediated renal diseases. Since the reciprocal relationship between IL-6 and chemokines in renal inflammation has been barely investigated, we have analyzed whether IL-6 (500 ng/ml), alone or in combination with the soluble form of its receptor (sIL-6R, 200 ng/ml), can induce normal human mesangial cells (NHMC) to release alpha and/or beta chemokines: MCP-1 (monocyte chemoattractant protein 1), IL-8, Rantes (regulated on activation, normal T cell expressed and secreted), and MIP-1alpha (macrophage inflammatory protein 1alpha). Whereas IL-6 or sIL-6R alone were ineffective in inducing significant chemokine release from NHMC, the simultaneous treatment with IL-6 and sIL-6R showed a significant interaction, leading to a strong synergic effect on MCP-1 synthesis and release without exerting any relevant activity on IL-8, Rantes, or MIP-1alpha. Consistently with the unresponsiveness to IL-6, mRNA and protein expression analysis of the two subunits which form the functional IL-6 receptor showed that NHMC express only the gp130 signal-transducing chain and not the subunit-specific IL-6R (gp80). These findings support an unexpected role of the IL-6 system in kidney inflammatory reactions through the selective regulation of monocyte recruitment.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 1","pages":"37-43"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000059327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21499948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topographic distribution of aquaporin 2 mRNA in the kidney of dehydrated rats.","authors":"M Michimata,&nbsp;S Nogae,&nbsp;M Ohta,&nbsp;S Kaizuma,&nbsp;Y Imai,&nbsp;S Ito,&nbsp;M Matsubara","doi":"10.1159/000063279","DOIUrl":"https://doi.org/10.1159/000063279","url":null,"abstract":"<p><strong>Background: </strong>Stimulation of arginine vasopressin results in an immediate redistribution of water channels (aquaporin 2; AQP2) in the apical membrane of the collecting ducts, leading to water reabsorption. Water restriction for >/=24 h increases AQP2 proteins in the whole collecting duct which is highest in the inner medulla of the kidney, indicating that dehydration enhances synthesis of this protein. Although increased expression of AQP2 mRNA under this condition has been reported, the increased ratio of mRNA expression in the three regions of the kidney, cortex, outer medulla, and inner medulla, during the dehydration is still unclear.</p><p><strong>Methods: </strong>We investigated the AQP2 transcripts using male Sprague-Dawley rats deprived of water for 24 h. Mimic cDNA for competitive polymerase chain reaction (PCR) was constructed by deleting 180 bp at the middle of a 780-bp partial PCR product for rat AQP2 cDNA. In situ hybridization of the kidney and Northern blotting of inner medulla were performed using a 60-bp oligo-cDNA probe which identified rat AQP2 transcripts in the collecting duct.</p><p><strong>Results: </strong>Dehydration resulted in a significant increase in plasma osmolality and arginine vasopressin concentration and urinary osmolality. Competitive PCR demonstrated that dehydration increased AQP2 transcripts in all parts of the kidney, but was highest in the inner medulla. Northern blotting confirmed the high increased rate of AQP2 transcription in the inner medulla. In situ hybridization showed markedly intensified signals in the inner medulla of dehydrated rats.</p><p><strong>Conclusions: </strong>Our data indicate that dehydration increases the abundance of AQP2 transcripts which may be closely associated with enhancement in AQP2 protein synthesis reported previously. This topographically variable increase in transcription is considered to be one of the mechanisms involved in long-term regulation of water permeability in the collecting duct.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 1","pages":"28-36"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000063279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21499944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of changes in dietary intake of sodium and potassium and of metabolic acidosis on 11beta-hydroxysteroid dehydrogenase activities in rat kidney.","authors":"A Thompson,&nbsp;M A Bailey,&nbsp;A E Michael,&nbsp;R J Unwin","doi":"10.1159/000020647","DOIUrl":"https://doi.org/10.1159/000020647","url":null,"abstract":"<p><strong>Background/aim: </strong>Glucocorticoid activity is modulated by NADP(+)- and NAD(+)-dependent isoforms of the enzyme 11beta-hydroxysteroid dehydrogenase (11betaHSD) which convert glucocorticoids to their inactive metabolites. The NAD(+)-dependent isoform, 11betaHSD2, is present in the distal nephron where it confers aldosterone specificity on mineralocorticoid receptors. The objective of this study was to establish whether renal 11betaHSD activities are affected by changes in sodium and potassium balance and by metabolic acidosis.</p><p><strong>Methods: </strong>Renal 11betaHSD activities were measured ex vivo from rats fed normal and high- and low-potassium diets and a low-sodium diet or given 1.5% NH(4)Cl to drink.</p><p><strong>Results: </strong>Rats maintained on high-potassium and low-sodium diets exhibited 59% (p < 0.01) and 28% (p < 0.05) decreases, respectively, in NAD(+)-dependent renal 11betaHSD activity (relative to rats fed control diet) with no changes in NADP(+)-dependent cortisol oxidation. Short-term (3 day) and longer-term (10 day) metabolic acidosis also decreased NAD(+)-dependent 11betaHSD activity by 50 and 52%, respectively, without affecting NADP(+)-dependent cortisol oxidation. The low-potassium diet had no detectable effect on renal 11betaHSD activities.</p><p><strong>Conclusion: </strong>These results suggest that adaptations to a high-potassium or a low-sodium diet and to metabolic acidosis involve decreases in renal 11betaHSD2 activity, enhancing the access of glucocorticoids to renal corticosteroid receptors.</p>","PeriodicalId":12179,"journal":{"name":"Experimental nephrology","volume":"8 1","pages":"44-51"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000020647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21499943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}