Abstract:
:Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis. Northern blot analysis indicated that thrombin induced an increase in the mRNA levels of t-PA and of PAI-1. We conclude that thrombin increases DNA synthesis in human mesangial cells and enhances the synthesis of both t-PA and PAI-1. The latter is released in a large excess as compared to t-PA. Hence, thrombin may have a role in provoking a localized hypofibrinolytic state and may contribute to the persistence of glomerular fibrin deposits during proliferative glomerulonephritis.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Villamediana LM,Rondeau E,He CJ,Medcalf RL,Peraldi MN,Lacave R,Delarue F,Sraer JDdoi
10.1038/ki.1990.297subject
Has Abstractpub_date
1990-11-01 00:00:00pages
956-61issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)57042-7journal_volume
38pub_type
杂志文章abstract::The inactivation of physiological glucocorticoids by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) confers mineralocorticoid specificity to certain aldosterone target tissues. Both NADP, and NAD-dependent isoforms of 11 beta-HSD have been described. An NAD-dependent isoform of 11 beta-HSD (11 beta-HSD2) was recen...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.39
更新日期:1996-01-01 00:00:00
abstract::We demonstrate that salts of diatrizoate and iothalamate, radiographic contrast agents, depress the active transport of sodium in the urinary bladder of the Columbian toad, Bufo marinus. Isolated toad bladders were incubated in isotonic Ringer's solutions with isosmolar displacement of sodium chloride by contrast medi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.11
更新日期:1975-02-01 00:00:00
abstract:BACKGROUND:The underlying mechanisms of renal transplant dysfunction are poorly understood. There is little information on tubular function in kidney grafts. The cDNAs encoding kidney-specific cell surface proteins required for renal reabsorption of sodium (sodium cotransporter in thick ascending limb of Henle, rBSC1) ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.060002672.x
更新日期:2001-08-01 00:00:00
abstract::The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.340
更新日期:1992-09-01 00:00:00
abstract::The terminally differentiated podocyte, also called glomerular visceral epithelial cell, are highly specialized cells. They function as a critical size and charge barrier to prevent proteinuria. Podocytes are injured in diabetic and non-diabetic renal diseases. The clinical signature of podocyte injury is proteinuria,...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5000410
更新日期:2006-06-01 00:00:00
abstract:BACKGROUND:The feasibility of simultaneously infusing glucose and amino acid (AA)-based peritoneal dialysis solutions was tested to determine whether peritoneal dialysis patients could achieve an adequate nonprotein calorie/nitrogen ratio while preventing a marked increase in blood urea nitrogen (BUN), which is usually...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590051967.x
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Proteinase 3 is the major autoantigen in Wegener's granulomatosis (WG). Membrane PR3 expression is bimodal; low expressing cells (mPR3(low)) can be distinguished from cells with high expression (mPR3(high)) within a given individual. High mPR3 expression is a WG risk factor and is associated with relapse. Ho...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00640.x
更新日期:2004-06-01 00:00:00
abstract::Treatment of mesangial cells with recombinant human interleukin 1 beta (IL-1 beta) triggers the expression of a macrophage-type of nitric oxide (NO) synthase and the subsequent increase of cellular concentration of cGMP and nitrite production. Tetrahydrobiopterin (BH4) is an essential cofactor for NO synthase, and in ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.398
更新日期:1994-11-01 00:00:00
abstract::This study examined the expression of EPO, VEGF and VEGF receptor gene under conditions of reduced oxygen supply in primary cultures of rat hepatocytes, and compared it with the expression of these genes in hypoxic rat livers in vivo. To this end we exposed male Sprague-Dawley rats to hypoxia (10% and 8% O2), carbon m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.60
更新日期:1997-02-01 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: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::The defect in urinary acidification induced by amphotericin B (AMB) was further characterized in turtle bladder. Since AMB has been shown to increase the hydrogen ion (H+) permeability of this epithelium in the absence of exogenous bicarbonate ions (HCO3-), we explored the permeability characteristics in the presence ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.39
更新日期:1977-04-01 00:00:00
abstract:BACKGROUND:Gentamicin is commonly used in hemodialysis patients. Gentamicin pharmacokinetics during traditional hemodialysis have been described. Slow daily home (SDH) hemodialysis (7 to 9 hours a day/6 days a week) use is increasing due to benefits observed with increased hemodialysis. We determined gentamicin pharmac...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1046/j.1523-1755.2003.00819.x
更新日期:2003-03-01 00:00:00
abstract::Human mesangial cells (MC) in culture, when stimulated by interleukin 1 alpha(IL-1 alpha) or tumour necrosis factor (TNF alpha), but not with lipopolysaccharide (LPS), express interleukin 8 (IL-8) mRNA, and both cell associated and extracellular IL-8. Dexamethasone treatment of mesangial cells induced partial inhibiti...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.184
更新日期:1991-07-01 00:00:00
abstract::Diabetes mellitus is associated with natriuresis, whereas estrogen has been shown to be renoprotective in diabetic nephropathy and may independently regulate renal sodium reabsorption. The aim of this study was to determine the effects of 17-beta estradiol (E(2)) replacement to diabetic, ovariectomized (OVX) female ra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000140
更新日期:2006-02-01 00:00:00
abstract::Cultures of human proximal tubule cells were exposed to elevated concentrations of glucose and dome formation was assessed over a 22 day period of growth. Cultures grown on 5.5 mM glucose formed five domes per microscopic field while those exposed to elevated glucose concentrations (11.0 mM to 27.5 mM) formed only two...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.5
更新日期:1989-01-01 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
abstract::Recent decades have witnessed the revelation of expanding roles of the vitamin D endocrine system beyond calcium and phosphorus metabolism. Along with these non-calcemic or non-classic actions of vitamin D are newly discovered therapeutic actions of vitamin D analogs in a number of pathological conditions, including k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.175
更新日期:2010-07-01 00:00:00
abstract::Normal urine contains thousands of proteins, largely due to the presence of 'exosomes,' tiny vesicles secreted into the urine by renal epithelial cells. These exosomes, demonstrated by Keller and colleagues to be also retrievable from amniotic fluid, offer great promise for future disease biomarker discovery studies. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002510
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Although atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology. METHODS:Claims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00406.x
更新日期:2005-07-01 00:00:00
abstract::Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.10.038
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Transforming growth factor-beta (TGF-beta) is known to play an important role in the pathophysiology of renal tubular disease. Researchers have recently identified a novel mitogen-activated protein kinase kinase kinase (MAPKKK), TAK (TGF-beta activated kinase)1, which stimulates the MKK3/6-p38K pathway. The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00665.x
更新日期:1999-10-01 00:00:00
abstract::The purpose of this study was to explore risk factors affecting the incidence of chronic kidney disease (CKD) in general population. We conducted a 10-year follow-up study with 123 764 (male: 41 012, female: 82 752) adults aged 40 years and over who received community-based annual examinations. The primary outcome for...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002017
更新日期:2007-01-01 00:00:00
abstract::Clinical trials and experimental studies have highlighted the importance of epigenetic processes in the development of diabetic complications. One of the earliest features of diabetic nephropathy is renal enlargement. The epidermal growth factor (EGF) has a pivotal role in the development of diabetic nephromegaly and ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.39
更新日期:2011-06-01 00:00:00
abstract::Proteomics-based assays have substantially improved diagnostic accuracy in systemic amyloidosis and have led to the discovery of novel amyloidogenic proteins. The observation that human apolipoproteins are increasingly represented is intriguing and highlights the complex, and partially known, mutual effects of the mis...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.05.029
更新日期:2016-09-01 00:00:00
abstract::Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme, converting heme to biliverdin, during which iron is released and carbon monoxide (CO) is emitted; biliverdin is subsequently converted to bilirubin by biliverdin reductase. At least two isozymes possess HO activity: HO-1 represents the isozyme...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5001565
更新日期:2006-08-01 00:00:00
abstract::Tubulointerstitial nephritis (TIN) is a disease pattern with heterogeneous causes. Recently a specific subtype of autoimmune TIN, IgG4-related TIN, has been identified that is part of systemic IgG4-related disease/ autoimmune pancreatitis. On biopsy, this TIN shows an IgG4+ plasma cell-rich infiltrate, akin to the pan...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.342
更新日期:2010-11-01 00:00:00
abstract::EDTA (calcium disodium edetate) lead mobilization and x-ray fluorescence (XRF) finger bone lead tests were done in 42 patients with chronic renal failure and without persisting lead intoxication. Nineteen of 23 patients with gout and 8 of 19 without gout had positive EDTA lead mobilization tests. Those patients with g...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.175
更新日期:1984-09-01 00:00:00
abstract::In order to study the effects of acute ureteral obstruction on glomerular hemodynamics, glomerular hydrostatic capillary pressure (PG), pressure in the first-order peritubular capillaries (EAP), and intratubular pressure (PT) were directly measured in superficial nephrons on Munich-Wistar rats by micropuncture with a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.131
更新日期:1977-12-01 00:00:00
abstract:BACKGROUND:Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00392.x
更新日期:2004-02-01 00:00:00