Abstract:
:We examined the role of the plasminogen activator/plasmin system in extracellular matrix (ECM) degradation by human mesangial cells cultured on thin films of 125I-labeled ECM (Matrigel). ECM degradation (release of 125I into the medium) was dependent on exogenous plasminogen, proportional to the number of mesangial cells and amount of plasminogen added, and coincident with the appearance of plasmin in the medium. ECM degradation was completely blocked (P < 0.001) by two plasmin inhibitors, alpha-2-antiplasmin (40 micrograms/ml) and aprotinin (216 KIU/ml), and partially reduced (-33 +/- 1.8%, P < 0.01) by TIMP-1 (40 micrograms/ml), a specific inhibitor of matrix metalloproteinases. Zymography of medium obtained from cells cultured in the absence of plasminogen revealed the presence of latent matrix metalloproteinase-2 (MMP-2) which was converted to a lower molecular weight, active form in the presence of mesangial cells and plasminogen. Northern analysis of poly A+RNA prepared from cultured human mesangial cells revealed mRNA for tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA receptor (uPAR). The presence of uPA protein in medium obtained from cultured human mesangial cells was demonstrated by Western blotting and ELISA which revealed a large molar excess of PAI-1 (1.2 +/- 0.1 x 10(-9) M) over uPA (1.2 +/- 0.1 x 10(-12) M) and tPA (0.19 +/- 0.04 x 10(-9) M). ECM degradation was reduced by a monoclonal antibody (MAb) against human tPA (-54 +/- 8.6%) or human uPA (-39 +/- 5.2%) compared to cells treated with identical amounts of non-specific monoclonal IgG (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Baricos WH,Cortez SL,el-Dahr SS,Schnaper HWdoi
10.1038/ki.1995.150subject
Has Abstractpub_date
1995-04-01 00:00:00pages
1039-47issue
4eissn
0085-2538issn
1523-1755pii
S0085-2538(15)58914-Xjournal_volume
47pub_type
杂志文章abstract:BACKGROUND:Endothelium-derived nitric oxide and reactive oxygen species (ROS) have been proposed to regulate vascular tone by complex mechanisms, including the modulation of ion channel function. In endothelial function itself, activation of Ca2+-activated K+ channels (KCa) plays a crucial role by inducing hyperpolariz...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00051.x
更新日期:2003-07-01 00:00:00
abstract::During the heterologous phase of experimental anti-glomerular basement membrane (anti-GBM) nephritis, leukocyte influx peaks within hours, whereas albuminuria occurs within 1 day. In the subsequent autologous phase, endogenous anti-GBM IgG develops and albuminuria persists. Heparan sulfate (HS) proteoglycans like synd...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002514
更新日期:2007-11-01 00:00:00
abstract::Indomethacin antagonizes the natriuretic and chloruretic response to hydrochlorothiazide in most studies. Neither the mechanism nor nephron site of this antagonism has been determined. To identify sites and potential mechanisms, cortical micropuncture was performed during hydrochlorothiazide treatment in control and i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.114
更新日期:1987-05-01 00:00:00
abstract:BACKGROUND:The tissue renin-angiotensin system (RAS) may modulate the structural and functional changes that occur in the diabetic kidney. METHODS:Hypertensive transgenic (mREN-2)27 rat (TGR) that exhibit increased tissue renin expression were administered streptozotocin (STZ, diabetic) or citrate buffer (non-diabetic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00019.x
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:IgA nephropathy is the most common glomerular disease. Mechanisms leading to its occurrence and controlling the evolution of the disease remain largely unknown. Various genetic factors have been found, mostly implicating immunologically relevant genes (IgH, TCR, human lymphocyte antigen, and complement loci)...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00253.x
更新日期:2000-09-01 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::Micropuncture studies were carried out in surface nephrons of rats with nephrotoxic-serum (NTS)-induced nephrotic syndrome during a period of active sodium and water retention. It was found that hydrostatic pressure and tubular diameter were increased in the proximal tubules (13.4 +/- 0.2 vs. 10.4 +/- 0.2 mm Hg; 31.3 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1979.166
更新日期:1979-11-01 00:00:00
abstract:BACKGROUND:Inhibition of the renin-angiotensin system (RAS) prevents development of chronic allograft dysfunction in experimental animals. Whether this therapeutic approach is effective even if started when signs of allograft nephropathy are already manifested has not been investigated. METHODS:To address this issue, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00318.x
更新日期:2003-12-01 00:00:00
abstract::In experimental membranous nephropathy, antibody binding to glomerular epithelial cell membrane antigens results in complement activation and formation of complement C5b-9 membrane attack complexes in glomeruli. During active disease, the C5b-9 complexes are shed into the urine. To test the hypothesis that a similar m...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.242
更新日期:1991-09-01 00:00:00
abstract::Progressive renal fibrosis is the final common pathway leading to renal failure irrespective of the initiating cause. Clinical studies of renal fibrosis found that prominent mast cell accumulation correlated with worse outcomes. Mast cells are pluripotent innate immune cells that synthesize and secrete profibrotic med...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.211
更新日期:2012-09-01 00:00:00
abstract::Mesangial cells are known to secrete metalloproteinases that are capable of degrading the constituents of the GBM, and hence are potentially involved not only in the regular maintenance of the ECM components in the glomerulus, but also of contributing to any damage to these components that occurs in disease states. In...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.345
更新日期:1994-09-01 00:00:00
abstract::The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a s...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2011.118
更新日期:2011-08-01 00:00:00
abstract::Phagocyte-derived interleukin-12 (IL-12) is a key cytokine that induces the development of an effective Th1 type immune response in various inflammatory and infectious disorders. To determine the importance of IL-12 in the pathogenesis of autoimmune renal injury we examined the renal production of this heterodimeric c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.10
更新日期:1997-01-01 00:00:00
abstract::Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a sm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.188
更新日期:1992-05-01 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: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::Podocyte effacement and the reformation of foot processes and slit diaphragms can be induced within minutes experimentally. Therefore, it seems likely that the slit diaphragm proteins underlie orchestrated recycling mechanisms under the control of posttranslational modifiers. One of these modifiers, SUMO (small ubiqui...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.198
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:It is known that chronic renal insufficiency (CRI) patients with gout may have subtle lead poisoning. In addition, gout episodes frequently aggravate progressive renal insufficiency because of the use of nephrotoxic drugs and urate deposition. Our study was arranged to evaluate the causal effect of environme...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.00795.x
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND:Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy (RRT), concerns remain regarding the bioincompatible nature of standard PD fluid. In order to evaluate whether a newly formulated fluid of neutral pH, and containing low levels of glucose degradation products (GDP), resu...
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:10.1111/j.1523-1755.2004.00747.x
更新日期:2004-07-01 00:00:00
abstract::Insulin and growth factors activate the phosphatidylinositide-3-kinase pathway, leading to stimulation of several kinases including serum- and glucocorticoid-inducible kinase isoform SGK3, a transport regulating kinase. Here, we explored the contribution of SGK3 to the regulation of renal tubular phosphate transport. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.67
更新日期:2011-07-01 00:00:00
abstract::Potassium transport in the thick ascending limb is conducted by heterogeneous cells to opposite directions. Effects of glucocorticoids and mineralocorticoids on potassium transport of the rat medullary thick ascending limb (MTAL) were examined by in vitro microperfusion technique by measuring net potassium flux (JK), ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.122
更新日期:1995-03-01 00:00:00
abstract::Changes in macula densa intracellular pH (pHi) were used to monitor the direction of flux mediated by the apical Na:2Cl:K cotransporter. At the macula densa, a decrease in luminal [Cl] ([Cl]1) from 60 to 1 mM produced cellular alkalinization secondary to a cascade of events involving a decrease in apical Na:2Cl:K cotr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.115
更新日期:1995-03-01 00:00:00
abstract::We describe a rat model of renal failure that separates catabolic and anabolic states from each other. Muscle protein synthesis was compared during the anabolic period between sham (S) operated and renal failure (RF) rats that were fed different levels of dietary protein. Male rats weighing between 60 and 80 g first h...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.104
更新日期:1991-05-01 00:00:00
abstract::Nephropathy is among the most frequent complications of diabetes and the leading cause of end-stage renal disease. Despite the success of novel drugs in animal models, the majority of the subsequent clinical trials employing those drugs targeting diabetic nephropathy failed. This lack of translational value may in par...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.06.023
更新日期:2016-11-01 00:00:00
abstract::Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. The autophagy pathway is upregulated under stress conditions including cell starvation, hypoxia, nutrient and growth-factor deprivation, endoplasmic reticulum stress, and o...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2015.11.021
更新日期:2016-04-01 00:00:00
abstract:BACKGROUND:There is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-l beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF) in bone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00835.x
更新日期:2003-03-01 00:00:00
abstract:BACKGROUND:Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00440.x
更新日期:2000-12-01 00:00:00
abstract::Renal dysfunction is a common and serious complication in multiple myeloma (MM) patients. Renal proximal tubule injury is characteristic in MM, and may result in disturbed renal handling of various vitamins. The abnormal excretion of vitamins in urine may result in their low serum levels. The goal of this study was to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000024
更新日期:2006-01-01 00:00:00
abstract::In organ transplantation, ischemia/reperfusion (I/R) results in damage that may affect cell viability and lead to organ failure. I/R injury involves a complex cascade of events, including loss of energy, derangement of the ionic hemostasis, production of reactive oxygen species, and cell death. In this context, mitoch...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1111/j.1523-1755.2004.761_9.x
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:Cux-1 is a murine homeodomain protein that functions as a cell cycle-dependent transcriptional repressor in proliferating cells. Targets of Cux-1 repression include the cyclin kinase inhibitors p21 and p27. In the kidney, Cux-1 is spatially and temporally regulated, and ectopic expression of Cux-1 in transge...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.67099.x
更新日期:2005-02-01 00:00:00