Abstract:
BACKGROUND:Nuclear factor-kappaB (NF-kappaB) and activated protein-1 (AP-1) are transcription factors that regulate many genes involved in the progression of renal disease. Recent data have shown that NF-kappaB is activated in tubules and glomeruli in various experimental models of renal injury. In vitro studies also suggest that proteinuria could be an important NF-kappaB activator. We therefore approached the idea that NF-kappaB may be an indicator of renal damage progression. METHODS:Paraffin-embedded renal biopsy specimens from 34 patients with intense proteinuria [14 with minimal change disease (MCD) and 20 with idiopathic membranous nephropathy (MN)] and from 7 patients with minimal or no proteinuria (IgA nephropathy) were studied by Southwestern histochemistry for the in situ detection of activated transcription factors NF-kappaB and AP-1. In addition, by immunohistochemistry, we performed staining for the NF-kappaB subunits (p50 and p65) and AP-1 subunits (c-fos, c-jun). By immunohistochemistry and/or in situ hybridization, the expression of some chemokines [monocyte chemoattractant protein-1 (MCP-1), RANTES, osteopontin (OPN)] and profibrogenic cytokines [transforming growth factor-beta (TGF-beta)], whose genes are regulated by NF-kappaB and/or AP-1, were studied further. RESULTS:NF-kappaB was detected mainly in the tubules of proteinuric patients, but rarely in nonproteinuric IgA nephropathy (IgAN) patients. In addition, there was a significant relationship between the intensity of proteinuria and NF-kappaB activation in MCD (r = 0.64, P = 0.01) and MN patients (r = 0.64, P < 0.01). Unexpectedly, patients with MCD had a significantly higher NF-kappaB tubular activation than those with MN (P < 0.01). To assess whether there was a different composition of NF-kappaB protein components, immunostaining was performed for the NF-kappaB subunits p50 and p65. However, no differences were noted between MCD and MN patients. In those patients, there was a lower tubular activation of AP-1 compared with NF-kappaB. Moreover, a strong correlation in the expression of both transcription factors was observed only in MN (r = 0.7, P = 0.004). Patients with progressive MN had an overexpression of MCP-1, RANTES, OPN, and TGF-beta, mainly in the proximal tubules, while no significant expression was found in MCD patients. CONCLUSIONS:On the whole, our results show that a tubular overactivation of NF-kappaB and AP-1 and a simultaneous up-regulation of certain proinflammatory and profibrogenic genes are markers of progressive renal disease in humans. Increased activation of solely NF-kappaB and/or AP-1 may merely indicate the response of tubular renal cells to injury.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Mezzano SA,Barría M,Droguett MA,Burgos ME,Ardiles LG,Flores C,Egido Jdoi
10.1046/j.1523-1755.2001.00941.xsubject
Has Abstractpub_date
2001-10-01 00:00:00pages
1366-77issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)48004-4journal_volume
60pub_type
杂志文章abstract::Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small to detect treatment ef...
journal_title:Kidney international
pub_type:
doi:10.1016/j.kint.2017.04.019
更新日期:2017-08-01 00:00:00
abstract::The impact of early-diagnosed new-onset post-transplantation diabetes mellitus (PTDM) on cardiovascular (CV) disease is not well described. The objectives of the present prospective single-center observational study were to assess the long-term effects of early-diagnosed new-onset PTDM on major cardiac events (MCE; ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000116
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Aldosterone has been suggested to play a role in the initiation and progression of diabetic nephropathy. Currently recommended treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers [renin-angiotensin system (RAS) blockade] does not suppress circulating aldosterone ...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00756.x
更新日期:2005-12-01 00:00:00
abstract:BACKGROUND:The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.2001.00805.x
更新日期:2001-07-01 00:00:00
abstract::Colony stimulating factor-1 (CSF-1) is a chemoattractant and growth factor for macrophages. In autoimmune MRL-lpr mice, CSF-1 is detected in the circulation and there is an increase in CSF-1 transcripts and macrophages in the kidney. The purpose of this study was to establish whether the MRL-lpr kidney is responsible ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.9
更新日期:1996-01-01 00:00:00
abstract::The relationship of protein intake to urinary oxalate and glycolate excretion was examined in a large cohort (N = 101) of normal individuals on self-selected diets and in 11 individuals on controlled protein diets. On self-selected diets no correlation was detected between protein intake and urinary oxalate or glycola...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.253
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:Normal human podocytes are terminally differentiated and quiescent cells. It is not known why podocytes fail to proliferate in response to most forms of injury. Proliferation is regulated by cell cycle proteins and their inhibitors. The Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21, p27, p5...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00213.x
更新日期:2000-08-01 00:00:00
abstract::Vascular calcification is prevalent in dialysis patients and is associated with a high burden of cardiovascular disease. Fetuin-A is a potent inhibitor of vascular calcification, but the precise mechanism by which it mediates vascular calcification in uremia is unclear. Matsui and colleagues demonstrate that circulati...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2009.52
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00392.x
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Cellular and molecular mechanisms responsible for cisplatin-induced nephrotoxicity to renal tubular epithelial cells are not well understood. Although caspases play a critical role in the execution of the cell death pathway, their specific role in toxic injury to renal tubular epithelial cells has not been e...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00026.x
更新日期:2001-11-01 00:00:00
abstract::Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis involves innate and adaptive immune cells in the induction of autoimmunity and in autoimmune effector responses. Most Fcγ receptors (FcγRs) activate immune cells, but FcγRIIB, found in humans and mice on B cells and innate cells, is an inhibitor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.189
更新日期:2014-12-01 00:00:00
abstract::Although case reports link proton-pump inhibitor (PPI) use and hypomagnesemia, no large-scale studies have been conducted. Here we examined the serum magnesium concentration and the likelihood of hypomagnesemia (<1.6 mg/dl) with a history of PPI or histamine-2 receptor antagonist used to reduce gastric acid, or use of...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.452
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:Mice overexpressing thymic stromal lymphopoietin (TSLP) develop mixed cryoglobulinemia with renal disease closely resembling human cryoglobulin-associated membranoproliferative glomerulonephritis (MPGN), including glomerular deposits of immunoglobulins and complement. We assessed the effect of complement inh...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00495.x
更新日期:2004-04-01 00:00:00
abstract::Nephropathia epidemica (NE) caused by Puumala hantavirus is one type of hemorrhagic fever with renal syndrome (HFRS). There is considerable variability in the clinical severity of NE. Many infections are subclinical but the disease can even be fatal. We questioned whether the wide spectrum in the outcome of NE is depe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.29
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.00957.x
更新日期:2001-10-01 00:00:00
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
doi:10.1038/ki.1986.216
更新日期:1986-10-01 00:00:00
abstract:BACKGROUND:The T allele of the G protein beta3 subunit (GNB3) C825T polymorphism has been associated with increased signal transduction, increased activity of the kidney Na+/H+ exchanger, and also with late-onset essential hypertension. Hypertension is a strong independent risk factor for progression in IgA nephropathy...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00734.x
更新日期:2004-07-01 00:00:00
abstract::Intrarenal angiotensin II is increased in kidney diseases independently of plasma angiotensin II and is thought to promote progressive deterioration of renal architecture. Here we investigated the mechanism of enhanced renal angiotensin II generation in kidney glomerular diseases. For this, kidney- or liver-specific a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.453
更新日期:2014-05-01 00:00:00
abstract::To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and af...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.100
更新日期:1985-06-01 00:00:00
abstract::Protein-bound uremic toxins (PBUTs) accumulate in chronic kidney disease (CKD) and are poorly removed by dialysis. Gryp et al. demonstrated that fecal bacteria from patients with CKD do not produce more PBUTs than do those from healthy controls and that the accumulation of PBUTs, as CKD progresses, is mainly due to th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.02.026
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:Macrophage (Mphi) infiltration may contribute to chronic renal injury. We therefore sought to examine the expression of genes associated with Mphi recruitment in the rat remnant kidney model. METHODS:Male Munich Wistar rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no treatment ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00327.x
更新日期:2000-10-01 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:BACKGROUND:We evaluated the effects of different concentrations of iron dextran administered through the intraperitoneal route, in iron-deficient rats, on hematocrit (Hct in percentage), serum iron (mg/dL), total iron binding capacity (TIBC in mg/dL), and the function and histology of the peritoneal membrane. METHODS:...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002764.x
更新日期:2001-02-01 00:00:00
abstract::Vascular calcification (VC) is an important reason for the high burden of vascular disease among chronic dialysis patients. Chronic kidney disease (CKD) is associated with increased promoters and decreased inhibitors of VC. The circulating levels of fetuin-A, a well-described inhibitor of calcification, regulate the c...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/sj.ki.5002355
更新日期:2007-07-01 00:00:00
abstract::Gap junctions are present in the juxtaglomerular apparatus enabling intercellular communication. Our study determined the location of different connexin subtypes within the juxtaglomerular apparatus of the rat, and the role of these subtypes in renal hemodynamics through the use of specific mimetic peptides. Immunohis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002673
更新日期:2008-02-01 00:00:00
abstract:BACKGROUND:Phenylalanine is converted to para- and ortho-tyrosine by hydroxyl free radical, or to para-tyrosine by the phenylalanine hydroxylase enzyme. The aim of this study was to measure para- and ortho-tyrosine in the urine and plasma of patients with chronic renal disease and/or diabetes, to obtain information on ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00687.x
更新日期:2005-11-01 00:00:00
abstract::Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700–...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.323
更新日期:2016-03-01 00:00:00
abstract::Cyanate is a uremic toxin responsible for the carbamylation of proteins, which has been implicated as playing a key role in accelerating the progression of atherosclerosis in patients with chronic kidney disease. El-Gamal et al. report that while cyanate promotes protein carbamylation in vivo, the resulting endothelia...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.256
更新日期:2014-11-01 00:00:00
abstract::A protective role for sirtuin 6 (Sirt6) in the context of chronic renal injury is reported by Cai et al. in this issue of Kidney International. The mechanism is thought to be mediated by Sirt6's deacetylase activity, specifically on β-catenin target genes. This commentary discusses these results and the interaction be...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.09.022
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:The new oral microemulsion formulation of cyclosporine (Neoral) possesses superior pharmacokinetics to the conventional formulation, Sandimmun (SIM), providing more complete and predictable absorption, and less pharmacokinetic variability. METHODS:The safety and tolerability of Neoral, together with the inc...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1523-1755.1998.00042.x
更新日期:1998-09-01 00:00:00