Abstract:
:Recent evidence suggesting a strong interplay between components of the renin-angiotensin system and key mediators of fibrosis led us to hypothesize that renin, independent of its enzymatic action to enhance angiotensin (Ang) II synthesis, directly increases production of the fibrogenic cytokine transforming growth factor (TGF)-beta. Human or rat mesangial cells (MCs) were treated with human recombinant renin (HrRenin) or rat recombinant renin (RrRenin) and the effects on TGF-beta1, plasminogen activator inhibitor-type 1 (PAI-1), fibronectin (FN) and collagen 1 mRNA and protein were investigated. Blockade of the rat MC renin receptor was achieved using siRNA. HrRenin or RrRenin, at doses shown to be physiologically relevant, induced marked dose- and time-dependent increases in TGF-beta1. These effects were not altered by adding an inhibitor of renin's enzymatic action (RO 42-5892), the Ang II receptor antagonist losartan or the Ang-converting enzyme inhibitor enalapril. RrRenin also induced PAI-1, FN and collagen 1 mRNA and PAI-1 and FN protein in a dose-dependent manner. Neutralizing antibodies to TGF-beta partially blocked these effects. Supernatant and cell lysate Ang I and Ang II levels were extremely low. MC angiotensinogen mRNA was undetectable both with and without added renin. Targeting of the rat renin receptor mRNA with siRNA blocked induction of TGF-beta1. We conclude that renin upregulates MC TGF-beta1 through a receptor-mediated mechanism, independent of Ang II generation or action. Renin-induced increases in TGF-beta1 in turn stimulate increases in PAI-1, FN and collagen I. Thus, renin may contribute to renal fibrotic disease, particularly when therapeutic Ang II blockade elevates plasma renin.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Huang Y,Wongamorntham S,Kasting J,McQuillan D,Owens RT,Yu L,Noble NA,Border Wdoi
10.1038/sj.ki.5000011subject
Has Abstractpub_date
2006-01-01 00:00:00pages
105-13issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)51309-4journal_volume
69pub_type
杂志文章abstract::Efficacy and safety of antibiotic 'locks', in prevention of thrombotic and infectious complication-related morbidity and mortality, among diabetics dialyzed through tunneled-cuffed catheters (TCCs) has not been effectively investigated. This trial was designed to investigate the outcome of TCCs (n = 109), inserted amo...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001776
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:Elevated glucose levels and glomerular hypertension (Pgc) are considered to contribute to the elaboration of matrix protein by mesangial cells (MCs) in diabetic glomeruli. MCs grown in 30 mM of glucose produce excessive matrix protein, as do MCs exposed to cyclic strain, and the combination of the two exacer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00743.x
更新日期:1999-11-01 00:00:00
abstract::Erythropoiesis stimulating agent (ESA) treatment has been a major advance in the care of patients with kidney disease, resulting in reduced symptoms and blood transfusions, and improved quality of life. Recent studies, however, have indicated that attempts to treat to near normal Hgb targets may result in increased ri...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2008.467
更新日期:2009-02-01 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: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
doi:10.1046/j.1523-1755.2001.00795.x
更新日期:2001-07-01 00:00:00
abstract::Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular h...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2015.306
更新日期:2016-03-01 00:00:00
abstract::To determine whether the induction of immune-mediated glomerular injury influences the formation of cyclooxygenase products by glomerular cells, we determined prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) (as the stable metabolite of TXA2) formation in isolated glomeruli of rats with passive Heymann nephritis (PHN...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.118
更新日期:1987-05-01 00:00:00
abstract:BACKGROUND:Increasing proteinuria in kidney disease is associated with an increased risk of renal failure. Urinary proteins such as albumin induce inflammatory signaling and gene expression in tubular epithelial cells (TECs). Fibronectin is an extracellular matrix protein that can exist in soluble form and is excreted ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00667.x
更新日期:2005-11-01 00:00:00
abstract::Absorption of amino acids by the necturus proximal tubules was measured under free-flow conditions The coexistence of proximal tubular amino acid influx was determined by infusing saline into tubular lumens by the stopped-flow microperfusion technique. Under free-flow conditions, fractional absorption of individual am...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.67
更新日期:1978-06-01 00:00:00
abstract::A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.368
更新日期:1994-10-01 00:00:00
abstract::Melamine, a widely used chemical found in many products in daily use, became a public health concern due to melamine-associated urinary stone formation in children. In adults, it is still unknown whether low-dose melamine exposure may also cause urolithiasis. To address this question, we studied 211 Taiwanese patients...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.154
更新日期:2011-10-01 00:00:00
abstract::Tissandié and colleagues report in this issue on their studies of IgA1 glycosylation and biological activities of IgA1-containing circulating immune complexes in patients with alcoholic cirrhosis who developed secondary renal disease with IgA deposits, secondary IgA nephropathy. Their seminal findings demonstrate abno...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2011.302
更新日期:2011-12-01 00:00:00
abstract::Neutrophil gelatinase-associated lipocalin (Ngal, 24p3, SIP24, lipocalin 2, or siderocalin) was originally purified from neutrophils, but with unknown function. Recently, it was identified that Ngal activates nephron formation in the embryonic kidney, is rapidly and massively induced in renal failure and possesses kid...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002165
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND:Wegener's granulomatosis (WG) is a rare systemic autoimmune disease characterized by small-vessel vasculitis leading to organ damage and the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). ANCAs were shown to be involved in the pathogenesis of the disease by increasing adhesion of polymorphonu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00430.x
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:The peritoneum is progressively denuded of its mesothelial cell monolayer in patients on continuous ambulatory peritoneal dialysis (CAPD). These alterations of the mesothelium cause membrane dysfunction and progressive peritoneal fibrosis. Integrins regulate cell motility and play an important role in wound ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00772.x
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:Tumor necrosis factor (TNF)-alpha rapidly primes neutrophils (PMN) for an anti-neutrophil cytoplasmic antibody (ANCA)-induced respiratory burst and is thus proinflammatory. TNF-alpha also progressively accelerates apoptosis. We investigated the effect of TNF-alpha-mediated apoptosis on ANCA antigen expressio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00161.x
更新日期:2002-02-01 00:00:00
abstract:BACKGROUND:Transplantation is the optimal therapy for pediatric end-stage renal disease (ESRD) patients, but in a subset of patients with peritoneal membrane failure, failed transplants or poor social situations, chronic hemodialysis (HD) remains the only option. Long-term survival of arteriovenous fistulas (AVFs) and ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00630.x
更新日期:2002-11-01 00:00:00
abstract::Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.04.031
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Genetic polymorphisms of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes are associated with increased risk of hypertension and left ventricular hypertrophy (LVH) in hypertensive subjects. However, the extent to which these polymorphisms are related to LVH and remodeling in dialysis p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00933.x
更新日期:2003-05-01 00:00:00
abstract::A new study in dialysis patients demonstrates that more than one-third of rehospitalizations within 30 days of discharge occur within the first week, and these rehospitalizations are associated with worse survival. Imposing a penalty on the dialysis provider for these rehospitalizations, as mandated by the Hospital Re...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.046
更新日期:2017-10-01 00:00:00
abstract::We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hyperte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002796
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND:Proteomic techniques have recently become available for large-scale protein analysis. The utility of these techniques in identification of urinary proteins is poorly defined. We constructed a proteome map of normal human urine as a reference protein database by using two differential fractionated techniques ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2002.kid565.x
更新日期:2002-10-01 00:00:00
abstract::Patients with chronic renal failure frequently have hypogonadism. To elucidate the molecular mechanisms involved, we tested the ability of serum from these patients to inhibit recombinant human luteinizing hormone receptors. Using a cell line expressing functional human luteinizing hormone receptors, we found that ade...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.109
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Home nocturnal hemodialysis is an intensive form of hemodialysis, where patients perform their treatments at home for about 7 hours approximately 6 nights a week. Compared with in-center conventional hemodialysis, home nocturnal hemodialysis has been shown to improve physiologic parameters and reduce health ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00157.x
更新日期:2003-09-01 00:00:00
abstract::Kallistatin is a serine protease inhibitor with anti-inflammatory, anti-angiogenic, and anti-oxidative properties. Since oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy, we studied the effect and mechanisms of action of kallistatin superinduction. Using ultrasound-microbubble-mediate...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.331
更新日期:2016-02-01 00:00:00
abstract::Ischemia-reperfusion occurs in a great many clinical settings and contributes to organ failure or dysfunction. CD154-CD40 signaling in leukocyte-endothelial cell interactions or T-cell activation facilitates tissue inflammation and injury. Here we tested a siRNA anti-CD40 in rodent warm and cold ischemia models to che...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.146
更新日期:2015-09-01 00:00:00
abstract::From September 9 to October 3, 1994, five patients on maintenance hemodialysis in a dialysis unit in Tokyo contracted hepatitis B virus (HBV) infection successively, and four of them died of fulminant hepatitis. The unit treated 181 patients three times a week on eight shifts, and all five afflicted patients were on t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.499
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND:It is known that inhibition of cyclooxygenase (COX) impairs the renal actions of loop diuretics. Recently, we found that cyclosporine A (CsA) inhibits renal COX-2 expression. Therefore, we examined the interferences of CsA with the renal actions of loop diuretics. METHOD:We investigated the renal effects of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00627.x
更新日期:2004-06-01 00:00:00
abstract::Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.6
更新日期:1976-01-01 00:00:00
abstract:BACKGROUND:Cardiovascular death continues to be a major problem in renal failure. Structural abnormalities of the heart and the vasculature contribute to the increased cardiovascular risk. They are ameliorated by angiotensin-converting enzyme (ACE) inhibitors, but because of the nonspecifity of ACE inhibition, it is un...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00163.x
更新日期:2000-07-01 00:00:00