Abstract:
BACKGROUND:Tubulointerstitial inflammation and fibrosis are pathologic hallmarks of end-stage renal disease (ESRD). Here we have used DNA microarray technology to monitor the transcriptomic responses to murine unilateral ureteral obstruction (UUO) with a view to identifying molecular modulators of tubulointerstitial fibrosis. METHODS:Using Affymetrix Mu74Av2 microarrays, gene expression 4 and 10 days postobstruction was investigated relative to control contralateral kidneys. Candidate profibrogenic genes were further investigated in epithelial cells undergoing epithelial to mesenchymal transition (EMT) in vitro. RESULTS:mRNA levels for 1091 gene/EST sequences, of a total of 12,488 displayed on the microarray, were altered twofold or greater by days 4 and 10 postobstruction compared to contralateral control kidneys. Genes were categorised into functional groups, including modulators of cytoskeletal and extracellular matrix metabolism, cell growth, signalling, and transcription/translational events. Among the potentially profibrogenic genes, whose mRNA levels were increased after UUO, were fibroblast-inducible secreted protein (fisp-12), the murine homologue of connective tissue growth factor (CTGF), collagen XVIIIalpha1, secreted protein acidic and rich in cysteine (SPARC), and src-suppressed C-kinase substrate (SSeCKS). A sustained increase in fisp-12 mRNA level was observed during EMT induced by transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF). CONCLUSION:Altered gene expression in murine UUO has been demonstrated. Increased expression of fisp-12, SPARC, and SSeCKS has been shown in response to TGF-beta1 treatment and during EMT, suggesting that these genes may offer potential therapeutic targets against tubulointerstitial fibrosis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Higgins DF,Lappin DW,Kieran NE,Anders HJ,Watson RW,Strutz F,Schlondorff D,Haase VH,Fitzpatrick JM,Godson C,Brady HRdoi
10.1046/j.1523-1755.2003.00306.xsubject
Has Abstractpub_date
2003-12-01 00:00:00pages
2079-91issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49576-6journal_volume
64pub_type
杂志文章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:BACKGROUND:Cadaveric renal transplantation is associated with a survival advantage compared with dialysis patients remaining on the renal transplantation waiting list, but this advantage has not been confirmed in obese end-stage renal disease (ESRD) patients. METHODS:Using data from the USRDS, we studied 7521 patients...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00761.x
更新日期:2003-02-01 00:00:00
abstract::The presence of CR1 mRNA in podocytes was investigated using a 35S-labeled CR1 cDNA probe and in situ hybridization in sections from fetal and adult human kidneys. CR1 mRNA was only detected in immature podocytes at early stages of glomerular differentiation in the fetal kidney. In contrast, CR1 antigen was abundantly...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.198
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:Recently, we observed that the severity of glomerulonephritis in an experimental model of immunoglobulin A nephropathy (IgAN) induced by Sendai virus differs between C57BL/6 and BALB/c mouse strains. The determinants of differing renal insufficiency are not understood. In the present study, we examine the ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00258.x
更新日期:2003-11-01 00:00:00
abstract::The interaction of 15-hydroxyeicosatetraenoic acid (15-HETE) and cultured MDCK renal tubular epithelial cells was investigated to determine whether incorporation of this lipoxygenase product will affect polyphosphoinositide formation. MDCK cells were incubated with 1 microM [3H]-15-HETE for 15 to 120 minutes. Maximum ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.131
更新日期:1994-04-01 00:00:00
abstract::Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1 infection, is infrequently associated with renal dysfunction and biopsy findings of acute tubular necrosis. We examined the clinical and pathological findings in 13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1±9.6...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.318
更新日期:2010-12-01 00:00:00
abstract::We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.119
更新日期:1993-04-01 00:00:00
abstract::In six healthy males on a fixed sodium/potassium (Na/K) intake, we studied the relation between plasma K and urine K and Na excretion after an oral K load. Studies were repeated during fludrocortisone (0.5 mg bid) or spironolactone (50 mg qid), that is, after escape from the Na-retaining and Na-excreting effects of th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.235
更新日期:1988-11-01 00:00:00
abstract::Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xe...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.66
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:Evaluation of beta2-microglobulin (beta2m) removal during hemodialysis using predialysis and immediate postdialysis plasma concentrations is only valid in the absence of postdialysis rebound. Postdialysis rebound of beta2m has not been studied extensively, and its importance in the determination of beta2m cl...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.1999.00669.x
更新日期:1999-10-01 00:00:00
abstract::Mitochondria are critical in determining a cell's energy homeostasis and fate, and mitochondrial dysfunction has been implicated in the pathogenesis of chronic kidney disease (CKD). We sought to identify causative mitochondrial microRNAs. A microarray screen of kidney tissue from healthy mice identified 97 microRNAs t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.12.028
更新日期:2019-06-01 00:00:00
abstract::Hyperlipidemia can induce or aggravate renal tubulointerstitial injury. Experiments in a complex rat model with chronic glomerulonephritis and long-standing, coexisting hyperlipidemia suggested that induction of xanthine oxidase (XO), with increased oxygen radical generation, is involved in aggravation of tubulointers...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000121
更新日期:2006-02-01 00:00:00
abstract:BACKGROUND:Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00420.x
更新日期:1999-05-01 00:00:00
abstract::Rare autosomal dominant tubulointerstitial kidney disease is caused by mutations in the genes encoding uromodulin (UMOD), hepatocyte nuclear factor-1β (HNF1B), renin (REN), and mucin-1 (MUC1). Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Ju...
journal_title:Kidney international
pub_type: 共识发展会议,杂志文章,实务指引
doi:10.1038/ki.2015.28
更新日期:2015-10-01 00:00:00
abstract::Segerer et al. report the expression and localization of macrophage and dendritic-cell markers in human renal biopsies and indicate that both cell types express CD68, findings that resonate with murine studies. The functional and phenotypic distinction between macrophages and dendritic cells is discussed. ...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.189
更新日期:2008-07-01 00:00:00
abstract::The existence of a tissue renin-angiotensin (RAS) system independent of the circulating RAS has prompted the search for cellular binding sites for angiotensinogen and for renin in order to explain their tissue uptake. Two receptors that bind with similar affinity mature renin and prorenin were identified, the mannose-...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000265
更新日期:2006-05-01 00:00:00
abstract::Vitamin D receptor agonists (VDRAs) inhibit the renin-angiotensin system (RAS) and reduce podocyte loss and fibrosis over and above RAS blockade. Several studies in humans show that VDRAs are antiproteinuric and have the potential to delay the progression of renal disease. Whether VDRAs will accomplish this goal among...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.77
更新日期:2010-06-01 00:00:00
abstract::Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.122
更新日期:1983-07-01 00:00:00
abstract::To test the contribution of bicarbonate (Bi) to hemodynamic stability during hemodialysis (HD), we compared the effects of ultrafiltration dialysis with bicarbonate and with acetate under conditions of high-sodium (141 mEq/liter) and low-sodium (130 mEq/liter) dialysate concentrations in 12 stable HD patients. Group 1...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1984.134
更新日期:1984-07-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to evaluate the renoprotective effect as reflected by short-term changes in albuminuria of ultrahigh doses of irbesartan in type 2 diabetic patients with microalbuminuria. METHODS:This double-masked randomized crossover trial included 52 (41 males) hypertensive type 2 diabetic ...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1523-1755.2005.00511.x
更新日期:2005-09-01 00:00:00
abstract:BACKGROUND:Idiopathic nephrotic syndrome is a proteinuric disease secondary to the release of a nonidentified circulating glomerular permeability factor by T cells. Because specificities of T-cell activation in idiopathic nephrotic syndrome remain unknown, we evaluated transcriptional activation of T cells in nephrotic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00322.x
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:Endotoxin is an important factor in the development of acute renal failure related to infection and in acceleration of chronic nephritis. Lipopolysaccharide (LPS; the major component of endotoxin) is one of the most potent triggers for renal cells to produce monocyte chemoattractant protein-1 (MCP-1), a key ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00051.x
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND:The podocyte is the focus of much research into the mechanisms of renal disease progression, and the number of podocytes per glomerulus has thus become a parameter of much interest. When counting podocytes, the actual particle counted is the cell nucleus. The majority of published studies estimating podocyte...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1111/j.1523-1755.2004.00787.x
更新日期:2004-08-01 00:00:00
abstract::Current practice recommends metabolic evaluation of patients who have formed multiple renal stones, but not those with one stone or temporally remote stones. This presumes that recentness and recurrence imply greater risk of new future stones. We hypothesize that number of stones reflects how long patients are permitt...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.224
更新日期:1994-06-01 00:00:00
abstract::We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized t...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2010.352
更新日期:2011-01-01 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: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::How the dialysis dose is normalized is just one of several assumptions that clinicians need to take into account when prescribing peritoneal dialysis. El-Kateb et al. confirm that estimating the volume of urea distribution is associated with significant error and show that energy expenditure is not linearly related to...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2016.09.020
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Gene expression profiling of nephropathies may facilitate development of diagnostic strategies for complex renal diseases as well as provide insight into the molecular pathogenesis of kidney diseases. To test molecular based renal disease categorization, differential gene expression profiles were compared be...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00499.x
更新日期:2004-03-01 00:00:00
abstract::Anti-NDP has been detected in the sera of 38 of 430 patients on regular hemodialysis at the Regional Kidney Disease Program in Minneapolis. It developed in these patients from 7 to 58 months after commencement of dialysis. Bacterial infection appeared temporally related to the development of anti-NDP in 12 patients. H...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.133
更新日期:1976-12-01 00:00:00