DNAzyme for TGF-beta suppressed extracellular matrix accumulation in experimental glomerulonephritis.


BACKGROUND:We developed an electroporation-mediated gene transfer method targeting glomerular mesangial cells. Injecting DNA solution via renal artery followed by electric pulses using tweezers-type electrodes could result in efficient transfection in mesangial cells. Therefore, this gene transfer system opened a feasible strategy to manipulate the function of several cytokines and growth factors in mesangial cells. Recently, a new generation of catalytic nucleic acid composed of DNA, named DNA enzyme (DNAzyme), has been developed. METHOD:We generated a DNAzyme (TGFDE) targeting transforming growth factor-beta1 (TGF-beta1), and examined the therapeutic effect of TGFDE in vitro and in vivo. RESULTS:In cultured rat mesangial cells, treatment with TGFDE blocked TGF-beta1 mRNA expression, and thereby suppressed type I collagen mRNA expression. Next, we introduced TGFDE or scrambled DNAzyme (TGFSCR) into anti-Thy-1 model of nephritic rats by electroporation 3 days after disease induction. Northern blot analysis and immunohistochemical staining demonstrated that glomerular message and protein expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), and type I collagen were suppressed in TGFDE-transfected nephritic rats compared with untreated nephritic rats and TGFSCR-transfected rats on day 7. Consequently, we observed significant reduction in glomerular matrix score in TGFDE-transfected nephritic rats. CONCLUSION:Inhibition of TGF-beta1 expression by electroporation-mediated DNAzyme transfer might be useful for the therapy of glomerulonephritis.


Kidney Int


Kidney international


Isaka Y,Nakamura H,Mizui M,Takabatake Y,Horio M,Kawachi H,Shimizu F,Imai E,Hori M




Has Abstract


2004-08-01 00:00:00














  • The International Pediatric Peritonitis Registry: starting to walk.

    abstract::The International Pediatric Peritonitis Registry (IPPR) was created to assess and evaluate the validity of the pediatric peritonitis treatment guidelines issued by the International Society for Peritoneal Dialysis. The study by Schaefer et al., one of the first to emerge from the IPPR, describes regional variability i...

    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Teitelbaum I

    更新日期:2007-12-01 00:00:00

  • Small proteoglycans of normal adult human kidney: distinct expression patterns of decorin, biglycan, fibromodulin, and lumican.

    abstract:BACKGROUND:Among the members of the small leucine-rich proteoglycan family, decorin, biglycan, and fibromodulin have been proposed to be potent modulators of transforming growth factor-beta (TGF-beta) activity, thereby playing an important role in the pathogenesis of fibrotic kidney diseases. Furthermore, decorin expre...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Schaefer L,Gröne HJ,Raslik I,Robenek H,Ugorcakova J,Budny S,Schaefer RM,Kresse H

    更新日期:2000-10-01 00:00:00

  • Kidney transplant nephrotic syndrome: relationship between allograft histopathology and natural course.

    abstract::We analyzed clinical and pathologic data from 36 recipients of 38 renal allografts who developed nephrotic syndrome following transplantation. Three groups were identified on the basis of histologic changes in the graft, and each group had a distinct clinical course. Nine grafts (23.7%) had recurrent glomerulonephriti...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Cheigh JS,Mouradian J,Susin M,Stubenbord WT,Tapia L,Riggio RR,Stenzel KH,Rubin AL

    更新日期:1980-09-01 00:00:00

  • Visualization of renal autoregulation in the split hydronephrotic kidney of rats.

    abstract::The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit tech...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Steinhausen M,Blum M,Fleming JT,Holz FG,Parekh N,Wiegman DL

    更新日期:1989-05-01 00:00:00

  • Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy.

    abstract:BACKGROUND:The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjec...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章


    authors: Lacourcière Y,Bélanger A,Godin C,Hallé JP,Ross S,Wright N,Marion J

    更新日期:2000-08-01 00:00:00

  • Differential expression of Cux-1 and p21 in polycystic kidneys from Pkd1 null and cpk mice.

    abstract:BACKGROUND:Cux-1 is a murine homeodomain protein that functions as a cell cycle-dependent transcriptional repressor in proliferating cells. Targets of Cux-1 repression include the cyclin kinase inhibitors p21 and p27. In the kidney, Cux-1 is spatially and temporally regulated, and ectopic expression of Cux-1 in transge...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Sharma M,Brantley JG,Alcalay NI,Zhou J,Heystek E,Maser RL,Vanden Heuvel GB

    更新日期:2005-02-01 00:00:00

  • Methicillin-resistant Staphylococcus aureus nasal carriage and infections in CAPD.

    abstract::In view of the increasing concern about methicillin-resistant Staphylococcus aureus (MRSA) infections, we studied the characteristics and outcome of MRSA nasal carriage and infections in our CAPD program. All patients entering into the CAPD program from January 1989 to December 1991 were enrolled into the study. The p...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Lye WC,Leong SO,Lee EJ

    更新日期:1993-06-01 00:00:00

  • Coronary artery stenosis: a new risk factor for chronic kidney injury?

    abstract::Coronary artery stenosis induces renal inflammation and kidney injury in pigs even in the absence of myocardial infarction or clinically significant heart failure. This effect is aggravated by experimentally induced renovascular hypertension. Interestingly, oxidative stress originating from the ischemic myocardium was...

    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Rump LC,Stegbauer J

    更新日期:2015-04-01 00:00:00

  • A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy.

    abstract::IgA nephropathy (IgAN) is the most prevalent primary chronic glomerular disease for which no safe disease-specific therapies currently exist. IgAN is an autoimmune disease involving the production of autoantigenic, aberrantly O-glycosylated IgA1 and ensuing deposition of nephritogenic immune complexes in the kidney. A...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Myette JR,Kano T,Suzuki H,Sloan SE,Szretter KJ,Ramakrishnan B,Adari H,Deotale KD,Engler F,Shriver Z,Wollacott AM,Suzuki Y,Pereira BJG

    更新日期:2019-07-01 00:00:00

  • Lead chelation therapy and urate excretion in patients with chronic renal diseases and gout.

    abstract:BACKGROUND:It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environme...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Lin JL,Yu CC,Lin-Tan DT,Ho HH

    更新日期:2001-07-01 00:00:00

  • A role for novel cell-cycle proteins in podocyte biology.

    abstract::Cell-cycle proteins influence almost all aspects of embryogenesis and differentiation. In adults, these proteins control cell division and regeneration after injury. During the past several years, their roles in controlling reaction to stress have been demonstrated in several organ systems. In the kidney, the cell typ...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Price PM

    更新日期:2010-04-01 00:00:00

  • Amylin deposition in the kidney of patients with diabetic nephropathy.

    abstract::Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in the development of beta-cell dysfunction in patients with diabetes; however, the involvement of amylin in renal amyloidosis has not been studied. For this reason, we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Gong W,Liu ZH,Zeng CH,Peng A,Chen HP,Zhou H,Li LS

    更新日期:2007-07-01 00:00:00

  • Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients.

    abstract::Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mi...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Bhan I,Powe CE,Berg AH,Ankers E,Wenger JB,Karumanchi SA,Thadhani RI

    更新日期:2012-07-01 00:00:00

  • Kidney cancer: identification of novel targets for therapy.

    abstract::Kidney cancer, although relatively rare when compared to other malignancies, occurs not uncommonly in patients with renal disease and is often discovered incidentally during the initial nephrologic work-up, or by the savvy clinician who is familiar with the paraneoplastic signs. While surgical approaches are generally...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Weiss RH,Lin PY

    更新日期:2006-01-01 00:00:00

  • Prognostic value of inducible myocardial ischemia in predicting cardiovascular events after renal transplantation.

    abstract:BACKGROUND:The aims of the present study were to determine the prevalence of inducible myocardial ischemia (IMI) in renal transplant recipients (RTR) more than 50 years old, to identify predictors of IMI, and to search for its prognostic value. METHODS:Among the 377 renal transplantations performed between 1989 and 19...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Dussol B,Bonnet JL,Sampol J,Savin B,De La Forte C,Mundler O,Habib G,Morange S,Barrau K,Loundoun A,Vacher-Coponat H,Berland Y

    更新日期:2004-10-01 00:00:00

  • Effect of a high NaCl diet on the active mechanisms of Na+ extrusion in rat kidney.

    abstract::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Marín R,Obando MA,Proverbio T,Proverbio F

    更新日期:1986-10-01 00:00:00

  • Expression of fibroblast growth factors and their receptors in rat glomeruli.

    abstract::Fibroblast growth factors (FGFs) regulate cell proliferation and differentiation, and are also important regulators of extracellular matrix. They are among the most potent angiogenic factors known. Evidence suggests the FGFs play a role in glomerular development and pathology. The aim of the present study was to deter...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Ford MD,Cauchi J,Greferath U,Bertram JF

    更新日期:1997-06-01 00:00:00

  • Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors.

    abstract::We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Huang HS,Chen J,Chen CF,Ma MC

    更新日期:2006-08-01 00:00:00

  • Increased nitric oxide inactivation by reactive oxygen species in lead-induced hypertension.

    abstract:BACKGROUND:We have recently found evidence for increased reactive oxygen species (ROS) in rats with lead-induced hypertension. We hypothesized that increased ROS activity may contribute to hypertension by enhancing inactivation of nitric oxide (NO) in this model. METHODS:Rats were treated for 12 weeks with either lead...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Vaziri ND,Liang K,Ding Y

    更新日期:1999-10-01 00:00:00

  • Role of epidermal growth factor receptor in acute and chronic kidney injury.

    abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase. Its activation results in beneficial or detrimental consequences, depending on the particular setting. Earlier studies in the animal model of acute kidney injury showed that EGFR activation promotes renal tubular cell proliferation. Activation of E...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Tang J,Liu N,Zhuang S

    更新日期:2013-05-01 00:00:00

  • Short-term vitamin D receptor activation increases serum creatinine due to increased production with no effect on the glomerular filtration rate.

    abstract::Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates, raising concerns that its use may be detrimental to kidney function. Here we studied the effect of vitamin D receptor activation on serum creatinine, creatinine generation, and its clear...

    journal_title:Kidney international

    pub_type: 临床试验,杂志文章


    authors: Agarwal R,Hynson JE,Hecht TJ,Light RP,Sinha AD

    更新日期:2011-11-01 00:00:00

  • Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study.

    abstract:BACKGROUND:Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS:This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Young EW,Albert JM,Satayathum S,Goodkin DA,Pisoni RL,Akiba T,Akizawa T,Kurokawa K,Bommer J,Piera L,Port FK

    更新日期:2005-03-01 00:00:00

  • If you lose your nerves, at least you will not get kidney fibrosis!

    abstract::Kidney fibrosis is one of the most promising treatment targets in nephrology. To design effective treatment approaches, a detailed understanding of the initiating mechanisms is of great importance. Kim and Pandanilam now find that renal nerves are a major trigger for renal fibrosis. Both afferent and efferent nerve fi...

    journal_title:Kidney international

    pub_type: 评论,杂志文章


    authors: Boor P,Papasotiriou ME

    更新日期:2015-02-01 00:00:00

  • Tissue engineering of a bioartificial renal tubule assist device: in vitro transport and metabolic characteristics.

    abstract:BACKGROUND:Current renal substitution therapy for acute or chronic renal failure with hemodialysis or hemofiltration is life sustaining, but continues to have unacceptably high morbidity and mortality rates. This therapy is not complete renal replacement therapy because it does not provide active transport nor metaboli...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Humes HD,MacKay SM,Funke AJ,Buffington DA

    更新日期:1999-06-01 00:00:00

  • p21(WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth.

    abstract:BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Dusso AS,Pavlopoulos T,Naumovich L,Lu Y,Finch J,Brown AJ,Morrissey J,Slatopolsky E

    更新日期:2001-03-01 00:00:00

  • Factors in the dialysis regimen which contribute to alterations in the abnormalities of uremia.

    abstract::While hemodialysis therapy in its present form is capable of sustaining life, dialysis patients are not metabolically normal and we are unable to say what technical factors contribute adequate therapy. Recent efforts to resolve these problems have led to the assumption that substances in the molecular weight range of ...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Lowrie EG,Steinberg SM,Galen MA,Gagneux SA,Lazarus JM,Gottlieb MN,Merrill JP

    更新日期:1976-11-01 00:00:00

  • Solitary functioning kidney and diverse genital tract malformations associated with hepatocyte nuclear factor-1beta mutations.

    abstract:BACKGROUND:Renal tract malformations are, on occasion, associated with uterine malformations. The transcription factor hepatocyte nuclear factor (HNF)-1beta is expressed from the earliest stages of development of the Wolffian duct, the mesonephros and metanephros, and the Müllerian ducts in the mouse. In adult mice HNF...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Bingham C,Ellard S,Cole TR,Jones KE,Allen LI,Goodship JA,Goodship TH,Bakalinova-Pugh D,Russell GI,Woolf AS,Nicholls AJ,Hattersley AT

    更新日期:2002-04-01 00:00:00

  • Mouse kidney expresses mRNA of four highly related sodium-glucose cotransporters: regulation by cadmium.

    abstract:BACKGROUND:To study the molecular mechanism responsible for cadmium-induced Fanconi syndrome, an in vitro mouse model has been used. We have previously shown that exposure of primary cultures of kidney cortical cells to micromolar concentrations of cadmium inhibited uptake of the glucose analog, [14C] methyl alpha-d-gl...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Tabatabai NM,Blumenthal SS,Lewand DL,Petering DH

    更新日期:2003-10-01 00:00:00

  • Changes in plasma 1,25 and 24,25-dihydroxyvitamin D after renal transplantation in children.

    abstract::The purpose of this investigation is to analyze changes in plasma 1,25-(OH)2D and 24,25-(OH)2D after successful renal transplantation in 20 children and young adults. Studies were performed on 8 subjects between the 1st and 10th month and on 12 others between the 20th and 30th to 36th month. Samples were assayed for p...

    journal_title:Kidney international

    pub_type: 杂志文章


    authors: Garabedian M,Silve C,Levy-Bentolila D,Bourdeau A,Ulmann A,Nguyen TM,Lieberherr M,Broyer M,Balsan S

    更新日期:1981-09-01 00:00:00

  • Antioxidant therapy in hemodialysis patients: a systematic review.

    abstract::Antioxidants have been used as therapies to decrease oxidative stress and improve CVD risk in hemodialysis (HD) patients. A systematic search of the Medline database (search date 30 April 2011) found 56 studies investigating the effects of antioxidant therapies on biomarkers of oxidative stress (53 studies) or clinica...

    journal_title:Kidney international

    pub_type: 杂志文章,评审


    authors: Coombes JS,Fassett RG

    更新日期:2012-02-01 00:00:00