Abstract:
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.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Isaka Y,Nakamura H,Mizui M,Takabatake Y,Horio M,Kawachi H,Shimizu F,Imai E,Hori Mdoi
10.1111/j.1523-1755.2004.00777.xsubject
Has Abstractpub_date
2004-08-01 00:00:00pages
586-90issue
2eissn
0085-2538issn
1523-1755pii
S0085-2538(15)50085-9journal_volume
66pub_type
杂志文章abstract:BACKGROUND:Bicarbonate reabsorption in the kidney proximal tubule is predominantly mediated via the apical Na+/H+ exchanger (NHE-3) and basolateral Na+: HCO(-3) cotransporter (NBC-1). The purpose of these studies was to examine the effects of Na+ load and altered acid-base status on the expression of NHE-3 and NBC-1 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00995.x
更新日期:2001-11-01 00:00:00
abstract::Previous work has documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheter...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.223
更新日期:1992-06-01 00:00:00
abstract::Experiments in rodents have demonstrated an important role for selectins in kidney ischemia-reperfusion injury (IRI). However, the relevance of this in larger mammals, as well as the impact on long-term structure and function is unknown. We tested the hypothesis that small molecule selectin ligand inhibition attenuate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000335
更新日期:2006-05-01 00:00:00
abstract::The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.31
更新日期:1991-02-01 00:00:00
abstract::Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the p...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.368
更新日期:2015-03-01 00:00:00
abstract::Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in chil...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.401
更新日期:2008-10-01 00:00:00
abstract::Kidney disease is associated with increased cardiovascular morbidity, but underlying mechanisms are poorly understood. We tested the hypothesis that chronic renal insufficiency impairs angioadaptation in a rat model of hindlimb ischemia. Twenty male Sprague-Dawley rats (8 weeks old) underwent subtotal nephrectomy (5/6...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000448
更新日期:2006-06-01 00:00:00
abstract::The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjecte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.230
更新日期:1995-06-01 00:00:00
abstract::It is unknown whether the association between body mass index (BMI) and chronic kidney disease (CKD) is mediated by genetic confounding or obesity-associated diabetes. We investigated the association between BMI and incident CKD in 29,136 Swedish twins with no history of CKD or diabetes, first using traditional Cox re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.12.019
更新日期:2019-05-01 00:00:00
abstract:UNLABELLED:Expression of apoptosis regulatory genes in chronic cyclosporine nephrotoxicity favors apoptosis. BACKGROUND:Chronic cyclosporine (CsA) nephrotoxicity is characterized by interstitial fibrosis, tubular dropout, and loss of cellularity in areas of fibrosis. Apoptosis was found to play a role in CsA-induced f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00794.x
更新日期:1999-12-01 00:00:00
abstract::We have developed an immunological procedure for measuring advanced glycosylation end-products (AGEs) in serum. Using this method, we measured AGEs in healthy volunteers, patients with diabetes, renal failure without treatment and in patients with renal failure, treated with hemodialysis (HD) or continuous ambulatory ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.262
更新日期:1994-07-01 00:00:00
abstract::Highly presensitized patients wait longer for a renal allograft than unsensitized patients and have a poorer allograft survival rate. Repeated blood transfusions have been implicated in the induction and maintenance of sensitization. To determine the effect of recombinant human erythropoietin (rHuEPO) therapy on five ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.161
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND:An Experimental model of proliferative glomerulonephritis induced by an antibody against Thy-1 antigen has been established. However, the pathophysiologic role and the critical epitope of Thy-1 molecule for induction of mesangial cell dysfunction remain unknown. We have reported that monoclonal antibody 1-22...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.66011.x
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a pati...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00572.x
更新日期:1999-08-01 00:00:00
abstract::Urinary exosomes have received considerable attention as a potential biomarker source for the diagnosis of renal diseases. Notwithstanding, their use in protein biomarker research is hampered by the lack of efficient methods for vesicle isolation, lysis, and protein quantification. Here we report an improved ultracent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.25
更新日期:2012-06-01 00:00:00
abstract::Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammaso...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.271
更新日期:2015-01-01 00:00:00
abstract::We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.08.024
更新日期:2021-01-01 00:00:00
abstract::Many features of chronic kidney disease may be reversed, but it is unclear whether advanced lesions, such as adhesions of sclerotic glomerular tufts to Bowman's capsule (synechiae), can resolve during treatment. We previously showed, using a renal ablation model, that the renoprotective effect of the AT-1 receptor blo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.528
更新日期:2009-01-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) are key mediators of adverse peritoneal membrane remodeling in peritoneal dialysis eventually leading to ultrafiltration failure. Both are pleiotropic growth factors with cell type-dependent regulation of expression and biological eff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.217
更新日期:2013-12-01 00:00:00
abstract::Obesity could affect associations between creatinine generation, estimated body surface area, and excretory burden, with effects on chronic kidney disease assessment. We therefore examined the impact of obesity on the performances of estimated glomerular filtration rate (eGFR), the urine albumin:creatinine ratio (ACR)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.112
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:Caveolin is a principal component of caveolae and regulates signaling in caveolae. Mesangial cells contain many caveolae, and thus manipulation of caveolin-1 expression level might be useful to control mesangial cell proliferation, which is an important aggravating factor in many renal diseases. METHODS:In ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00954.x
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:This study evaluated the effects of dietary sodium manipulation in dogs on the regulation of canine angiotensin receptors (cAT1 and cAT2) in the kidney and adrenal. METHODS:Isolated glomeruli and membranes from renal medulla and the adrenal gland were used in radioligand binding assays from two groups of do...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051881.x
更新日期:2001-05-01 00:00:00
abstract::The relationship between body mass index (BMI) and end-stage renal disease (ESRD) is confounded by co-morbidities associated with both conditions. Furthermore, the association at low range BMI is controversial. We studied this association in the Singapore Chinese Health Study, a population-based prospective cohort tha...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.03.019
更新日期:2017-10-01 00:00:00
abstract::Hemodynamic studies were performed at two levels of dietary sodium intake (10 mmoles/day and 100 mmoles/day for 14 days) in a group of patients (with retained kidneys) on chronic hemodialysis. Plasma renin activity and aldosterone, plasma, and extracellular fluid (ECF) volumes were measured while the patient were at r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.114
更新日期:1977-10-01 00:00:00
abstract::Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Dep...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.42
更新日期:2011-06-01 00:00:00
abstract::Vitamin D deficiency is common in patients with chronic kidney disease after renal transplantation. Vitamin D, essential for mineral and bone metabolism, also has myriad beneficial autocrine effects on intact immune responses and defense against infection, as well as suppression of malignant changes. Supplementation w...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.492
更新日期:2009-03-01 00:00:00
abstract::Thrombomodulin (TM), an endothelial receptor for thrombin, endowed with a powerful anticoagulant activity, plays an important role in the antithrombogenicity of the vascular endothelium. Its presence within the human renal glomerulus is already known but was thought to be only endothelial. We looked for TM expression ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.99
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Immune response to oxidized low-density lipoprotein (oxLDL) may modulate the process of atherogenesis and cardiovascular disease. METHODS:We performed a prospective, observational cohort study in 249 patients with end-stage renal disease (ESRD) to examine whether the serum titer of anti-oxLDL antibody can p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00692.x
更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF-A) is expressed constitutively in the adult glomerular podocytes at high levels; however, the regulation of its production is unclear. Recent data from podocyte-specific knockout mice suggest that VPF/VEGF-A is critical for the proper ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00910.x
更新日期:2004-10-01 00:00:00
abstract::The kidney is influenced by circadian rhythms and is entrained to the sleep-wake cycle allowing anticipation of the metabolic and physiological demands of the kidney throughout a 24-hour cycle. Although sleep disruption has been studied extensively in cardiovascular and metabolic disease, its association with chronic ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2015.12.048
更新日期:2016-06-01 00:00:00