Nephron Extra最新文献_第10页

Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury. Fas配体对缺血性急性肾损伤的凋亡和炎症的影响大于TNF-α。

Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-02-03 DOI: 10.1159/000335533

Kengo Furuichi, Satoshi Kokubo, Akinori Hara, Ryu Imamura, Qiang Wang, Shinji Kitajima, Tadashi Toyama, Toshiya Okumura, Kouji Matsushima, Takashi Suda, Naofumi Mukaida, Shuichi Kaneko, Takashi Wada

{"title":"Fas Ligand Has a Greater Impact than TNF-α on Apoptosis and Inflammation in Ischemic Acute Kidney Injury.","authors":"Kengo Furuichi, Satoshi Kokubo, Akinori Hara, Ryu Imamura, Qiang Wang, Shinji Kitajima, Tadashi Toyama, Toshiya Okumura, Kouji Matsushima, Takashi Suda, Naofumi Mukaida, Shuichi Kaneko, Takashi Wada","doi":"10.1159/000335533","DOIUrl":"https://doi.org/10.1159/000335533","url":null,"abstract":"Background/aim: Fas ligand (FasL) and tumor necrosis factor (TNF)-α are major pro-apoptotic molecules and also induce inflammation through cytokine and chemokine production. Although precise intracellular mechanisms of action have been reported for each molecule, the differential impact of these molecules on kidney injury in vivo still requires clarification.Methods: We explored the differential impact of FasL and TNF-α upon apoptosis and inflammation in ischemic acute kidney injury using neutralizing anti-FasL antibodies and TNF-α receptor 1 (TNFR1)-deficient mice.Results: TNFR1 deficiency was associated with a lesser anti-inflammatory effect upon leukocyte infiltration and tubular necrosis than treatment with anti-FasL antibody. Furthermore, the number of TUNEL-positive cells was significantly reduced in anti-FasL antibody-treated mice, whereas it was only partially diminished in TNFR1-deficient mice. In vitro studies confirmed these findings. FasL administration induced both apoptosis and cytokine/chemokine production from cultured tubular epithelial cells. However, TNF-α had a limited effect upon tubular epithelial cells.Conclusion: In ischemic acute kidney injury, FasL has a greater impact than TNF-α on the apoptosis and inflammatory reaction through cytokine/chemokine production from tubular epithelial cells.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"27-38"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000335533","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30554659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Premature aging of the microcirculation in patients with advanced chronic kidney disease. 晚期慢性肾病患者微循环过早衰老的研究

Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-11-21 DOI: 10.1159/000343295

Oanh H D Thang, Erik H Serné, Muriel P C Grooteman, Yvo M Smulders, Piet M Ter Wee, Geert-Jan Tangelder, Menso J Nubé

{"title":"Premature aging of the microcirculation in patients with advanced chronic kidney disease.","authors":"Oanh H D Thang, Erik H Serné, Muriel P C Grooteman, Yvo M Smulders, Piet M Ter Wee, Geert-Jan Tangelder, Menso J Nubé","doi":"10.1159/000343295","DOIUrl":"https://doi.org/10.1159/000343295","url":null,"abstract":"Background: Increasing age and advanced chronic kidney disease (CKD) are both associated with an attenuated vasodilator response of the skin microcirculation. In the present study, we investigated the effect of aging on microvascular reactivity in patients with advanced CKD.Methods: Acetylcholine (ACh)-mediated endothelium-dependent vasodilation and sodium nitroprusside (SNP)-mediated endothelium-independent vasodilation were assessed by iontophoresis combined with laser Doppler flowmetry. Microvascular function was compared between 52 patients with advanced CKD (stage 4-5: n = 16; end-stage renal disease: n = 36) and 33 healthy control subjects. As aging has an important effect on microvascular function, both control subjects and CKD patients were divided in subgroups younger and older than 45 years. Linear regression analysis was applied to assess potential associations between microvascular function and various demographic and clinical parameters.Results: There were three main findings. (1) In young patients with advanced CKD, both ACh- and SNP-mediated vasodilations were impaired if compared to young healthy controls (p = 0.04 and p = 0.056, respectively). (2) In young patients with advanced CKD, microvascular function was similar to old healthy controls and elderly patients with advanced CKD. (3) Whereas age was inversely associated with microvascular function in healthy controls (log ACh-mediated vasodilation R = -0.41; p = 0.02 and log SNP-mediated vasodilation R = -0.38; p = 0.03), no such relation was found in patients with advanced CKD.Conclusions: Our results are consistent with premature aging of the microvascular vasodilatory capacity in patients with advanced CKD.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"283-92"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000343295","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31127205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Typical Features of Amelogenesis Imperfecta in Two Patients with Bartter's Syndrome. 2例巴氏综合征无胚性发育不全的典型特征。

Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-12-18 DOI: 10.1159/000345801

Hercílio Martelli-Júnior, Shirlene Pimentel Ferreira, Paula Cristina B Pereira, Ricardo D Coletta, Sibele Nascimento de Aquino, Débora Marques Miranda, Ana Cristina Simões E Silva

{"title":"Typical Features of Amelogenesis Imperfecta in Two Patients with Bartter's Syndrome.","authors":"Hercílio Martelli-Júnior, Shirlene Pimentel Ferreira, Paula Cristina B Pereira, Ricardo D Coletta, Sibele Nascimento de Aquino, Débora Marques Miranda, Ana Cristina Simões E Silva","doi":"10.1159/000345801","DOIUrl":"https://doi.org/10.1159/000345801","url":null,"abstract":"Background/aims: Amelogenesis imperfecta (AI) is due to many inherited defects of enamel formation that affect the quantity and quality of enamel, leading to delay in tooth eruption and cosmetic consequences. AI has been described in association with nephrocalcinosis, which is called the enamel-renal syndrome. The aim of this case report is to describe typical features of AI in 2 patients with Bartter's syndrome (BS) for the first time.Methods: -Eight patients with confirmed BS were systematically screened for dental abnormalities as part of protocol. Those with suggestive clinical features of AI were submitted to panoramic X-ray and decayed teeth were analyzed by scanning electron microscopy.Results: Typical features of AI were detected in 2 girls with BS. These 2 patients showed nephrocalcinosis, and diagnosis and adequate clinical control were delayed. Genetic analysis detected the mutation responsible for BS in 1 of these patients. In this case, BS was due to a homozygous mutation of exon 5 of the KCNJ1 gene resulting in a substitution of valine for alanine at the codon 214 (A214V).Conclusions: The finding of typical features of AI in BS might constitute preliminary evidence that abnormalities of the biomineralization process found in patients with renal tubular disorders might also affect calcium deposition in dental tissues.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"319-25"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000345801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31176988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients. 日本透析患者的DNA高甲基化和炎症标志物。

Nephron Extra Pub Date : 2012-01-01 Epub Date: 2012-06-20 DOI: 10.1159/000339437

Sawako Kato, Bengt Lindholm, Peter Stenvinkel, Tomas J Ekström, Karin Luttropp, Yukio Yuzawa, Yoshinari Yasuda, Yoshinari Tsuruta, Shoichi Maruyama

{"title":"DNA hypermethylation and inflammatory markers in incident Japanese dialysis patients.","authors":"Sawako Kato, Bengt Lindholm, Peter Stenvinkel, Tomas J Ekström, Karin Luttropp, Yukio Yuzawa, Yoshinari Yasuda, Yoshinari Tsuruta, Shoichi Maruyama","doi":"10.1159/000339437","DOIUrl":"https://doi.org/10.1159/000339437","url":null,"abstract":"Background/aims: Inflammation is an established mortality risk factor in chronic kidney disease (CKD) patients. Although a previous report showed that uremic Caucasian patients with inflammation had signs of global DNA hypermethylation, it is still unknown whether DNA hypermethylation is linked to inflammatory markers including a marker of bacterial infections in Japanese CKD patients.Methods: In 44 consecutive incident dialysis patients (26 males, mean age 59 ± 12 years) without clinical signs of infection, global DNA methylation was evaluated in peripheral blood DNA using the HpaII/MspI ratio by the luminometric methylation assay method. A lower ratio of HpaII/MspI indicates global DNA hypermethylation. Procalcitonin (PCT), a marker of inflammation due to bacterial infections, was measured using an immunochromatographic assay.Results: The patients were divided into hyper- and hypomethylation groups based on the median value of the HpaII/MspI ratio 0.31 (range 0.29-0.37). Whereas patients in the hypermethylation group had higher ferritin levels [133.0 (51.5-247.3) vs. 59.5 (40.0-119.0) ng/ml; p = 0.046], there were no significant differences in age, gender, diabetes, smoking, anemia or serum albumin levels. However, the HpaII/MspI ratio showed significant negative correlations with PCT (ρ = -0.32, p = 0.035) and ferritin (ρ = -0.33, p = 0.027) in Spearman's rank test. In a multiple linear regression analysis, PCT and ferritin were associated with a lower HpaII/MspI ratio (R(2) = 0.24, p = 0.013).Conclusion: In this study, global DNA hypermethylation was associated with ferritin and, most likely, PCT, suggesting that inflammation induced by subclinical bacterial infection promoted DNA methylation.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"2 1","pages":"159-68"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000339437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30774011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Crescentic glomerulonephritis in IgA multiple myeloma: a case report. IgA多发性骨髓瘤合并月牙状肾小球肾炎1例。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-09-08 DOI: 10.1159/000331217

Grace T Moscoso-Solorzano, Marcus V Madureira-Silva, Carlos Balda, Marcello F Franco, Gianna Mastroianni-Kirsztajn

引用次数: 5

Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury. Smad与丝裂原活化蛋白激酶间的串扰调控环孢素A诱导的肾小管损伤的凋亡。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-10-26 DOI: 10.1159/000333014

Hideyuki Iwayama, Tatsuo Sakamoto, Akihiro Nawa, Norishi Ueda

{"title":"Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury.","authors":"Hideyuki Iwayama, Tatsuo Sakamoto, Akihiro Nawa, Norishi Ueda","doi":"10.1159/000333014","DOIUrl":"https://doi.org/10.1159/000333014","url":null,"abstract":"Background/aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs) and whether it regulates cyclosporine A (CyA)-induced apoptosis in renal proximal tubular cells (RPTCs).Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence) and apoptosis (determined by Hoechst 33258 staining) was examined in HK-2 cells.Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p)-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1-6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF) activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis.Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"1 1","pages":"178-89"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function. 甘露醇降低离体血灌注兔肾近端静水压力并改善其功能。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-11-04 DOI: 10.1159/000333478

Robbert Bipat, Paul Steels, Yves Cuypers, Jerry R Toelsie

{"title":"Mannitol Reduces the Hydrostatic Pressure in the Proximal Tubule of the Isolated Blood-Perfused Rabbit Kidney during Hypoxic Stress and Improves Its Function.","authors":"Robbert Bipat, Paul Steels, Yves Cuypers, Jerry R Toelsie","doi":"10.1159/000333478","DOIUrl":"https://doi.org/10.1159/000333478","url":null,"abstract":"Background/aims: Hypoxia may play a role in the development of renal failure in donated kidneys. In the present study, the effects of hypoxia on isolated blood-perfused rabbit kidneys were investigated and the effects of mannitol were explored, giving special attention to intratubular pressure.Methods: Kidneys were perfused with their autologous blood during four 30-min periods (P1-P4). P1 was considered baseline function. In P2, hypoxia was induced either alone or with an infusion of mannitol (15 mg/min) during P2-P4. Reoxygenation was applied after P2. Proximal intratubular pressure was measured in all conditions.Results: During hypoxia, renal blood flow doubled and restored immediately in P3. Urine flow stopped in P2, except in the series with mannitol, but gradually resumed in P3 and P4. Likewise, creatinine clearance recovered slightly (<25%) in P4, except for the series with mannitol, where it still could be measured in P2 and reached a value >50% of P1. Proximal intratubular pressure (mean ± SD) increased from 12 ± 5 in P1 to 24 ± 11 mm Hg during hypoxia and returned to 10 ± 6 mm Hg in P3. This increase was not observed with mannitol.Conclusion: Cellular swelling might be responsible for the suppressed filtration during hypoxia and can be prevented by mannitol.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"1 1","pages":"201-11"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach. 经逆行输尿管入路的腺相关病毒介导的基因转移至肾小管细胞。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-11-23 DOI: 10.1159/000333071

Daniel C Chung, Ben Fogelgren, Kwon Moo Park, Jessica Heidenberg, Xiaofeng Zuo, Liwei Huang, Jean Bennett, Joshua H Lipschutz

{"title":"Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach.","authors":"Daniel C Chung, Ben Fogelgren, Kwon Moo Park, Jessica Heidenberg, Xiaofeng Zuo, Liwei Huang, Jean Bennett, Joshua H Lipschutz","doi":"10.1159/000333071","DOIUrl":"https://doi.org/10.1159/000333071","url":null,"abstract":"Background/aims: Gene therapy involves delivery of exogenous DNA to provide a therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non-immunogenic, easy to produce, and efficient in protecting and delivering DNA into target cells.Methods: Adeno-associated virus (AAV) offers these advantages and few, if any, disadvantages, and over 100 isolates exist. We previously showed that AAV-mediated gene therapy can be used to restore vision to patients with Leber's congenital amaurosis, a disease of childhood blindness.Results: Here we show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with high efficiency both in vitroin cell culture and in vivoin mice. In addition, we adapted and modified a retrograde approach to allow for optimal transgene delivery to renal tubular cells that further minimizes the risk of an immunogenic reaction.Conclusions: We believe that recombinant AAV2, especially AAV2/8, gene delivery to renal tubule cells via a retrograde approach represents a viable method for gene therapy for a multitude of renal disorders ranging from autosomal dominant polycystic kidney disease to acute kidney injury.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"1 1","pages":"217-23"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26

Oxidative stress in cystinosis patients. 胱氨酸病患者的氧化应激。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-09-19 DOI: 10.1159/000331445

Maria Helena Vaisbich, Luciana Pache de Faria Guimaraes, Maria Heloisa Mazzola Shimizu, Antonio Carlos Seguro

{"title":"Oxidative stress in cystinosis patients.","authors":"Maria Helena Vaisbich, Luciana Pache de Faria Guimaraes, Maria Heloisa Mazzola Shimizu, Antonio Carlos Seguro","doi":"10.1159/000331445","DOIUrl":"https://doi.org/10.1159/000331445","url":null,"abstract":"Background/aims: Nephropathic cystinosis (NC) is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS) and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS) in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters.Methods: The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels.Results: We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p < 0.0001). We detected no significant correlation between plasma TBARS levels and renal function.Conclusion: An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"1 1","pages":"73-7"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000331445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear factor of activated T cells. 水通道蛋白-2启动子受活化T细胞的一氧化氮和核因子的协同调节。

Nephron Extra Pub Date : 2011-01-01 Epub Date: 2011-10-22 DOI: 10.1159/000333066

María F Albertoni Borghese, Layne M Bettini, Carlos H Nitta, Sergio de Frutos, Mónica Majowicz, Laura V Gonzalez Bosc

{"title":"Aquaporin-2 promoter is synergistically regulated by nitric oxide and nuclear factor of activated T cells.","authors":"María F Albertoni Borghese, Layne M Bettini, Carlos H Nitta, Sergio de Frutos, Mónica Majowicz, Laura V Gonzalez Bosc","doi":"10.1159/000333066","DOIUrl":"https://doi.org/10.1159/000333066","url":null,"abstract":"Background/aims: We have previously shown that aquaporin-2 (AQP2) is down-regulated in the renal medulla of rats made hypertensive by chronic inhibition of nitric oxide synthase. It has been shown that AQP2 expression is regulated by the calcineurin/nuclear factor of activated T cells (NFATc). Nitric oxide (NO) regulates the activity of NFATc via c-Jun-N-terminal kinase 2 (JNK2). Therefore, we hypothesized that increases in NO enhance NFATc-mediated up-regulation of AQP2 promoter activity.Methods: AQP2 mRNA and protein expression were detected in mouse renal papilla. AQP2 promoter luciferase reporter- and NFAT luciferase reporter-transfected MDCK cells were used to determine AQP2 promoter activity and NFATc activity, respectively. Cells were incubated with classic activators and inhibitors of NFATc and the NO pathway.Results: Our results demonstrate that both Ca(2+) and NO have a synergistic effect resulting in an increase in AQP2 mRNA and protein in mouse papilla and activation of the AQP2 promoter in kidney-derived cells. In addition, NO enhances Ca(2+)-induced NFATc activation. The underlying mechanism involves increased NFATc nuclear import and decreased export via protein kinase G-mediated inhibition of JNK1/2.Conclusions: This is the first study defining novel regulatory roles for NO and NFATc in the control of AQP2, which is an important renal protein.","PeriodicalId":56356,"journal":{"name":"Nephron Extra","volume":"1 1","pages":"124-38"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000333066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13