Abstract:
BACKGROUND:Cux-1 is a murine homeobox gene that is highly expressed in the nephrogenic zone of the developing kidney. Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with down-regulation of the cyclin kinase inhibitor p27. Because the reduction of p27 has been associated with mesangial cell proliferation and glomerular disease, we evaluated glomerular changes in Cux-1 transgenic mice. METHODS:Adult kidneys from Cux-1 transgenic mice were analyzed morphologically for changes in glomerular cell number and for changes in mesangial and interstitial extracellular matrix deposition. Mesangial matrix expansion was identified by light microscopy. Glomerular cell number was performed following immunohistochemistry. Type IV collagen deposition was analyzed by immunofluoresence and Western blotting. Renal function was evaluated by serum protein, blood urea nitrogen (BUN), creatinine, and electrolyte analysis, and by urine protein and creatinine analysis. RESULTS:In adult transgenic glomeruli, Cux-1 was ectopically expressed in mesangial cells, and this was associated with an increase in mesangial cell number, resulting from an increase in proliferation. There was a marked increase in mesangial matrix area in transgenic mice compared to non-transgenic littermates, related to an increase in type IV collagen. Podocyte foot process effacement was observed in transgenic mice, and this was related to an increase in urinary albumin. Interstitial fibrosis was also observed in transgenic kidneys. CONCLUSION:These observations indicate that increased expression of Cux-1 in mesangial cells results in cell proliferation and mesangial expansion. In addition, these changes are potentially related to disruption of podocyte architecture leading to loss of filtration. These results suggest that expression of Cux-1 is sufficient to induce the early events of mesangioproliferative glomerulonephritis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Brantley JG,Sharma M,Alcalay NI,Heuvel GBdoi
10.1046/j.1523-1755.2003.00889.xsubject
Has Abstractpub_date
2003-04-01 00:00:00pages
1240-8issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49002-7journal_volume
63pub_type
杂志文章abstract:BACKGROUND:This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids. METHODS:Phosphate binde...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1046/j.1523-1755.1999.00240.x
更新日期:1999-01-01 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
abstract:BACKGROUND:Rats that recover from acute puromycin nephrosis later develop widespread glomerular and tubulointerstitial injury. The current study sought to identify structural changes present in the recovery phase that could precipitate progressive renal disease. METHODS:Stereologic studies were performed 10 weeks afte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00481.x
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:Peritoneal sclerosis, characterized by collagen accumulation, is a serious complication in continuous ambulatory peritoneal dialysis (CAPD) therapy. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis. METHODS:We determined the expression...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00883.x
更新日期:2000-02-01 00:00:00
abstract::Defective recycling of megalin consequent to impaired phosphatidylinositol metabolism has been implicated as a mechanism causing tubular proteinuria in patients with Lowe syndrome. In this issue, Berquez et al. describe an innovative approach using a clinically approved drug to "rebalance" phosphatidylinositols and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.06.018
更新日期:2020-10-01 00:00:00
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
doi:10.1038/ki.2012.435
更新日期:2013-05-01 00:00:00
abstract::The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was asse...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.186
更新日期:1995-05-01 00:00:00
abstract::The molecular mechanism of Na+ and phosphate transport by the intestinal brush border membrane Na+/phosphate cotransporter was examined using anion and cation exchange columns interfaced to a light-activated microsecond timer. The nature of ion:cotransporter interaction was examined for sensitivity to itself versus no...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.141
更新日期:1996-04-01 00:00:00
abstract::The essential role of the glycoprotein hormone erythropoietin (Epo) in the control of red blood cell production is well established. Synthesis of Epo is induced in response to low oxygen (hypoxia). In response to stimulation, increases in serum Epo levels are paralleled by changes in the abundance of Epo mRNA. These c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.70
更新日期:1997-02-01 00:00:00
abstract::A major factor contributing to failure of arteriovenous fistulas (AVFs) is migration of smooth muscle cells into the forming neointima. To identify the source of smooth muscle cells in neointima, we created end-to-end AVFs by anastomosing the common carotid artery to the jugular vein and studied neural crest-derived s...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.73
更新日期:2015-09-01 00:00:00
abstract::Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of the...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1983.226
更新日期:1983-12-01 00:00:00
abstract:BACKGROUND:Renal inflammation is regulated by a network of local and systemic mediators. Of them, transforming growth factor-beta1 (TGF-beta 1) and glucocorticoids play an important role in deactivating monocytes/macrophages. We examined the hypothesis that TGF-beta 1 effects may be partially achieved through modulatio...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.63.6s.3.x
更新日期:2003-06-01 00:00:00
abstract::IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2018.02.030
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND:Chronic inflammation and oxidative stress are highly prevalent in patients with chronic kidney disease and end-stage renal disease (ESRD). These conditions contribute to high mortality rates associated with cardiovascular disease, the leading cause of death in this patient population. To our knowledge, no pr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00656.x
更新日期:2004-06-01 00:00:00
abstract:BACKGROUND:Since the cloning of the gene for autosomal dominant polycystic kidney disease type 2 (PKD2), approximately 40 different mutations of that gene have been reported to be associated with the disease. The relationship between the PKD2 genotype and phenotype, however, remains unclear. METHODS:Detailed clinical ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1046/j.1523-1755.2000.00989.x
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND:A considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated. METHODS:We studied retros...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.66027.x
更新日期:2004-12-01 00:00:00
abstract::The current study was undertaken to examine the effects of dithiothreitol (DDT), a sulfhydryl-reducing agent and heavy metal chelator, on the course of heavy metal-induced acute renal failure in the rat. Groups of rats in metabolic cages received uranyl nitrate (UN) alone, UN plus DTT, mercuric chloride (HgCl2) alone,...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.88
更新日期:1977-08-01 00:00:00
abstract::Proliferation of tubular epithelial cells underlies the development of cystic lesions and the subsequent impairment of renal function after renal mass reduction. The effect of HMG CoA reductase inhibitors (HRI) on cell proliferation was investigated in rat renal proximal tubular epithelial cells in primary culture. Tr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.423
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND:Microalbuminuria (MA) is a strong predictor of cardiovascular disease, but its causes are incompletely understood. Hyperhomocysteinemia is a recently recognized risk factor for cardiovascular disease independent of established risk factors. It is not known whether hyperhomocysteinemia is associated with MA, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.4495353
更新日期:1998-07-01 00:00:00
abstract::Serum calcitriol and the free calcitriol index together with factors considered to regulate calcitriol production were measured in eleven patients with moderate chronic renal failure (MCRF) and eleven age- and sex-matched normal subjects. Although the serum dialysable calcium levels were similar in the two groups, the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.58
更新日期:1988-03-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00317.x
更新日期:2000-10-01 00:00:00
abstract::The survival of patients with diabetes mellitus in the general population has improved in recent years. Here we assessed whether similar trends have occurred in 1688 kidney recipients, including 413 with diabetes prior to transplant between 1996 and 2007. Compared to patients without diabetes, the 5-year mortality was...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.70
更新日期:2014-09-01 00:00:00
abstract::Administration of antibody, directed against glomerular basement membrane (GBM) heparan sulfate-proteoglycan, into a presensitized rat results in the induction of membranous nephropathy with subepithelial immune-complex deposits. In this investigation, we examined the mechanisms responsible for the formation of subepi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.166
更新日期:1988-08-01 00:00:00
abstract::Recent insights have defined the central role of podocytes both in rare genetic diseases and as a general determinant of the progression of human glomerular diseases. In a recent issue of Nature, Weavers et al. described a podocyte-like cell type in Drosophila, the nephrocyte, that closely resembles mammalian podocyte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.653
更新日期:2009-03-01 00:00:00
abstract::The selective vasopressin V2-receptor antagonist tolvaptan is eliminated almost exclusively by non-renal mechanisms. As renal impairment can influence the pharmacokinetics of drugs even when eliminated by non-renal mechanisms, we evaluated the effect of renal insufficiency on the pharmacokinetics/pharmacodynamics of t...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.2013.350
更新日期:2014-04-01 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: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
doi:10.1046/j.1523-1755.1999.00486.x
更新日期:1999-06-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients. METHODS:A total of 275 (122 men and 153 women; aged 60.6 +/- 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00235.x
更新日期:2005-04-01 00:00:00
abstract::Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.08.013
更新日期:2018-02-01 00:00:00