Abstract:
BACKGROUND:Human mesothelial cells (HMCs) have an important role in maintaining an adequately functioning fibrinolytic system in the peritoneal cavity by secreting the fibrinolytic enzymes tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), as well as a specific PA inhibitor, PA inhibitor type 1 (PAI-1). In this study, we investigated whether the fibrinolytic capacity of HMCs is further counterbalanced by rapid uptake of t-PA and u-PA from the medium. METHODS:Cultured HMCs were used to study the uptake and degradation of radiolabeled t-PA and u-PA in the absence or presence of an inhibitor of cellular protein degradation, chloroquine, and of specific receptor antagonists. Northern blotting and ligand-blotting techniques were applied to demonstrate the presence of specific receptors for binding of t-PA and u-PA. RESULTS:At 37 degreesC, HMCs rapidly internalized and degraded 125I-t-PA and 125I-u-PA, which could be inhibited by an excess of unlabeled t-PA and u-PA, respectively, and by the lysosomotropic agent chloroquine. Northern blot analysis showed the expression of low-density lipoprotein (LDL) receptor-related protein (LRP), very low density lipoprotein (VLDL) receptor, and u-PA receptor. The addition of recombinant 39 kDa receptor-associated protein (RAP; an inhibitor of LRP and VLDL receptor) almost completely blocked the degradation of t-PA and partly that of u-PA. RAP ligand blotting demonstrated predominantly the presence of LRP, suggesting a major role for the LRP in mediating uptake and degradation of t-PA in HMCs. Endocytosis of u-PA occurs via two different pathways. After binding to u-PA receptor, a RAP-inhibitable and a non-RAP-inhibitable route for u-PA degradation was demonstrated. Tumor necrosis factor alpha (TNFalpha) diminished the fibrinolytic activity of HMCs by decreasing t-PA and increasing PAI-1 synthesis. The fall in t-PA levels could be counteracted by inhibiting t-PA degradation by either RAP or chloroquine. Interestingly, chloroquine also quenched the TNFalpha-induced changes in t-PA and PAI-1 mRNA levels. Using TNFalpha mutants and agonistic or blocking monoclonal antibodies specific for the TNF receptors p55 and p75, we found evidence that chloroquine interfered with the activation of the TNF receptor p55 and/or its intracellular signaling route. CONCLUSIONS:Receptor-mediated endocytosis plays a crucial role in regulating the fibrinolytic capacity of HMCs by its participation in the degradation of t-PA and u-PA, and in the TNFalpha-induced decrease in t-PA and the increase in PAI-1 expression.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sitter T,Toet K,Quax P,Kooistra Tdoi
10.1046/j.1523-1755.1999.00244.xsubject
Has Abstractpub_date
1999-01-01 00:00:00pages
120-9issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)30966-2journal_volume
55pub_type
杂志文章abstract:BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003855.x
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Controversy exists regarding the possible associations between a single nucleotide polymorphism of the transcobalamin II encoding gene (TCN2 776C>G) and plasma levels of vitamin B(12), folate, or total homocysteine. METHODS:In a cross-sectional study of 732 kidney allograft recipients, patients were categor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00592.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00732.x
更新日期:2003-01-01 00:00:00
abstract::Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001), we randomized 87 pro...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.ki.5001630
更新日期:2006-08-01 00:00:00
abstract::Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-ac...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.75
更新日期:1991-04-01 00:00:00
abstract::Proliferation of mesangial cells is frequently found in glomerulonephritis, such as IgA glomerulonephritis. Recent reports suggest that a brain/embryo-type myosin isoform (MIIB2) is involved in cell proliferation. We have studied the expression of MIIB2 in renal biopsy samples from patients with various renal diseases...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.191
更新日期:1996-05-01 00:00:00
abstract::Changes in tissue oxygen levels trigger molecular signaling pathways that regulate cellular proliferation and differentiation in multiple cell types. The functional role of oxygen signaling in the immune system is not well understood. Rama and colleagues demonstrate that hypoxia induces dendritic-cell maturation; thus...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.15
更新日期:2008-04-01 00:00:00
abstract::The processes of growth and remodeling that characterize growing bone are vulnerable to the biochemical effects of uremia. These processes are affected by the alterations in vitamin D metabolism and hyperparathyroidism that commonly occur with chronic renal insufficiency. Uremia interferes with cartilaginous developme...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1978.136
更新日期:1978-10-01 00:00:00
abstract:BACKGROUND:Bioimpedance, a noninvasive technique to analyze body composition, has attracted interest in determining body hydration in hemodialysis patients. However, the so-called whole-body (wrist-to-ankle) bioimpedance analysis (WBIA) is sensitive to changes in regional fluid distribution and tends to underestimate f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00588.x
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:Patients initiating dialysis after a failed kidney transplant are a subgroup of chronic kidney disease (CKD) patients who have not been characterized. Exposure to immunosuppressive medications differentiates these patients from the general incident end-stage renal disease (ESRD) population. METHODS:Data fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00373.x
更新日期:2002-06-01 00:00:00
abstract::It is no a secret that we are confronted by an alarmingly increasing number of patients with progressive renal disease. There is ample evidence for the notion that angiotensin II (Ang II) is a major culprit in progression. The vasopeptide Ang II turned out to have also multiple nonhemodynamic pathophysiologic actions ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2005.00145.x
更新日期:2005-03-01 00:00:00
abstract::Circulating parathyroid hormone (PTH) shows a complex relationship with hard outcomes in subjects with chronic kidney disease (CKD). Moreover, intervention studies directly targeting PTH failed to yield unequivocal results. Disturbed PTH metabolism, posttranslational modifications of PTH, and end-organ hyporesponsiven...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2016.06.041
更新日期:2016-12-01 00:00:00
abstract::The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjecte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.230
更新日期:1995-06-01 00:00:00
abstract::Fibroblast growth factor-23 (FGF23), a regulator of mineral metabolism, has been linked to cardiovascular disease in chronic kidney disease. As community-based data of the longitudinal association between FGF23 and cardiovascular events are lacking, we investigated a possible relationship in 727 men of the Uppsala Lon...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.327
更新日期:2013-01-01 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::The adaptation of erythropoietin production to oxygen supply is determined by the abundance of hypoxia-inducible factor (HIF), a regulation that is induced by a prolyl hydroxylase. To identify cells that express HIF subunits (HIF-1alpha and HIF-2alpha) and erythropoietin, we treated Sprague-Dawley rats with the prolyl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.460
更新日期:2010-02-01 00:00:00
abstract::Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated rena...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.215
更新日期:1991-08-01 00:00:00
abstract:BACKGROUND:Patients undergoing myeloablative allogeneic hematopoietic cell transplantation (HCT) have a high incidence of acute renal failure (ARF). However, it is unclear if ARF is independently associated with mortality after this procedure. METHODS:We performed meta-analysis of published reports on ARF after myeloa...
journal_title:Kidney international
pub_type: 杂志文章,meta分析
doi:10.1111/j.1523-1755.2005.00301.x
更新日期:2005-05-01 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::Cytokines and chemokines produced by tubular epithelial and infiltrating cells are critical to inflammation in renal ischemia-reperfusion injury. IL-37, a newly described IL-1 family member, inhibits IL-18-dependent pro-inflammatory cytokine production by its binding to IL-18 receptors and IL-18 binding protein. The p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.295
更新日期:2015-02-01 00:00:00
abstract::In previous studies from this laboratory it has been shown that ATP-ase activity in situ in the glomerular basement membrane (GBM) is clearly reduced in rats rendered nephrotic after treatment with adriamycin (ADR). The question was raised whether this reduction of ATP-ase activity in the GBM is due to toxic activity ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.55
更新日期:1987-03-01 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::Both single-frequency bioimpedance and multiple-frequency spectroscopy are equally accurate in measuring total-body water and intracellular fluid. Estimates are consistent at a population level but not at the individual level, because of wide limits of agreement. There is no real 'gold standard' method providing estim...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.434
更新日期:2014-04-01 00:00:00
abstract::The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.158
更新日期:1980-10-01 00:00:00
abstract::The widths of slit diaphragms in rat glomeruli were quantitatively measured on electron micrographs obtained by the rapid-freezing and freeze-substitution (FS) fixation method and compared to those prepared by conventional chemical fixation procedures, such as tannic acid, glutaraldehyde and osmium tetroxide (TGO) or ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.253
更新日期:1991-10-01 00:00:00
abstract::Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.ki.5000088
更新日期:2006-03-01 00:00:00
abstract::McAdoo et al. propose that patients with both circulating antiglomerular basement membrane antibody and antineutrophil cytoplasm antibody demonstrate a phenotype that lies between that of single-positive antiglomerular basement membrane disease and antineutrophil cytoplasm antibody-associated vasculitis. Specifically,...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.024
更新日期:2017-09-01 00:00:00
abstract::To verify the hypothesis that angiotensin-converting enzyme (ACE) inhibitors possess a unique renoprotective effect in progressive chronic renal disease, we decided to compare the effects of an ACE inhibitor and a calcium antagonist on both hypertension and the progression of non-diabetic renal insufficiency in a long...
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:10.1038/ki.1992.309
更新日期:1992-08-01 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::Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.19
更新日期:2012-07-01 00:00:00