Effect of Angiotensin II on Plasminogen Activator Inhibitor-1 Production by Cultured Human Mesangial Cells

Nephron ◽  
1997 ◽  
Vol 77 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Heather M. Wilson ◽  
Neva E. Haites ◽  
Nuala A. Booth
Keyword(s):  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Mesangial Cells ◽  
Activator Inhibitor

scholarly journals Salvia miltiorrhiza Depresses Plasminogen Activator Inhibitor-1 Production Through Inhibition of Angiotensin II

2008 ◽  
Vol 36 (05) ◽  
pp. 1005-1015 ◽  
Author(s):  
Jun Yuan ◽  
Xiaoqin Wang ◽  
Taohou Chen ◽  
Gang Chen ◽  
Yanfang Lu
Keyword(s):  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Mesangial Cells ◽  
Salvia Miltiorrhiza ◽  
Plasminogen Activator Inhibitor ◽  
Laser Scanning Microscopy ◽  
Ang Ii ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Pai 1

The purpose of this study was to investigate the effect of Salvia miltiorrhiza on the production of plasminogen activator inhibitor-1(PAI-1) induced by angiotensin II (Ang II) in renal mesangial cells. Rat mesangial cells were exposed to 100 nM Ang II. Meanwhile, different concentrations of Salvia miltiorrhiza injection were added to Mesangial Cells. PAI-1 mRNA was measured by semi-quantification reverse transcriptase polymerase chain reaction (RT-PCR) and PAI-1 protein by Western blotting. ELISA was used to detect the expression of transforming growth factor β1 (TGF-β1) in serum free MEM medium. The level of cellular reactive oxygen species (ROS) was measured by confocal laser scanning microscopy. Salvia miltiorrhiza notably attenuated expression of PAI-1 induced by Ang II in a concentration-dependent manner. Meanwhile, it suppressed the production of TGF-β1 and cellular ROS in mesangial cells. These effects were due to Salvia miltiorrhiza's ability of inhibiting the activities of angiotensin II. Therefore, Salvia miltiorrhiza can be used to retard progression of glomerular sclerosis.

scholarly journals Modulation of neutral protease expression in human mesangial cells by hyperglycaemic culture

1996 ◽  
Vol 320 (3) ◽  
pp. 777-783 ◽  
Author(s):  
Nadia ABDEL WAHAB ◽  
Roger M. MASON
Keyword(s):  
Plasminogen Activator ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Culture Conditions ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Mesangial Cells ◽  
Cell Matrix ◽  
Tissue Plasminogen ◽  
Protease Expression ◽  
Activator Inhibitor

We report on the effect of prolonged hyperglycaemic (11 and 30 mM d-glucose) culture conditions on human mesangial cell matrix metalloproteinases (MMPs), plasminogen activators and their inhibitors. The results indicate that hyperglycaemic conditions modulate the potential proteolytic activity of the enzymes secreted by confluent cultures of these cells. Gelatinase A (MMP-2) activity was always higher in cultures maintained under hyperglycaemic than under normoglycaemic conditions (4 mM d-glucose). In contrast, gelatinase B (MMP-9) activity was decreased under the same conditions. Matrilysin (MMP-7) activity was decreased by up to 100% under hyperglycaemic conditions. Reverse transcriptase–PCR and Western-blotting analyses indicate that in all cases both the transcripts and the protein level were correlated with enzymic activity.One tissue inhibitor of metalloproteinases, TIMP-2, was barely detectable under hyperglycaemic conditions (30 mM d-glucose). In contrast, TIMP-1 increased during the initial 2 weeks of culture in hyperglycaemic conditions and remained elevated to the end of the experiment (4 weeks). Under normoglycaemic conditions TIMP-1 decreased after 2 weeks of culture. Hyperglycaemic conditions also decreased markedly the activity of tissue plasminogen activator (t-PA). This seemed to be due to increased synthesis of its inhibitor, plasminogen activator inhibitor 1, under these conditions rather than to decreased expression of the t-PA enzyme.

Decorin suppresses transforming growth factor-β-induced expression of plasminogen activator inhibitor-1 in human mesangial cells through a mechanism that involves Ca2+-dependent phosphorylation of Smad2 at serine-240

2002 ◽  
Vol 362 (3) ◽  
pp. 643-649 ◽  
Author(s):  
Nadia ABDEL-WAHAB ◽  
Stephen J. WICKS ◽  
Roger M. MASON ◽  
Andrew CHANTRY
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Plasminogen Activator Inhibitor ◽  
Transforming Growth Factor Β ◽  
Receptor Activation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Human Mesangial Cells ◽  
Activator Inhibitor

Transforming growth factor-β (TGFβ) is a key mediator of extracellular matrix (ECM) accumulation in sclerotic kidney diseases such as diabetic nephropathy. One of the main target cells for TGFβ in the kidney are glomerular mesangial cells, which respond by increasing expression of ECM proteins, such as collagens, laminin and fibronectin, while suppressing the expression of ECM-degrading proteases and increasing the synthesis of ECM protease inhibitors, including plasminogen activator inhibitor-1. Previous studies have shown that exposure of mesangial cells to chronic high-glucose conditions, such as those seen in diabetes, increases ECM deposition in a mechanism involving glucose-mediated up-regulation of TGFβ expression. Naturally occurring inhibitors of this TGFβ-dependent fibrotic response include decorin, a small leucine-rich proteoglycan. While the mechanism by which TGFβ stimulates gene expression via the Smad signal-transduction pathway is becoming clear, the precise mechanism by which decorin may impinge upon TGFβ activity remains to be established. In this study, for the first time we provide evidence that decorin can disrupt glucose- and TGFβ/Smad-dependent transcriptional events in human mesangial cells through a mechanism that involves an increase in Ca2+ signalling, the activation of Ca2+/calmodulin-dependent protein kinase II and ensuing phosphorylation of Smad2 at Ser-240. We show that decorin also induces Ser-240 phospho-Smad hetero-oligomerization with Smad4 and the nuclear localization of this complex independently of TGFβ receptor activation. Thus, in human mesangial cells, the mechanism of decorin-mediated inhibition of TGFβ signalling may involve activation of Ca2+ signalling, the subsequent phosphorylation of Smad2 at a key regulatory site, and the sequestration of Smad4 in the nucleus.

scholarly journals Spironolactone Abolishes the Relationship between Aldosterone and Plasminogen Activator Inhibitor-1 in Humans

2002 ◽  
Vol 87 (2) ◽  
pp. 448-452 ◽  
Author(s):  
Pairunyar Sawathiparnich ◽  
Sandeep Kumar ◽  
Douglas E. Vaughan ◽  
Nancy J. Brown
Keyword(s):  
Angiotensin Ii ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Type Plasminogen Activator ◽  
Serum Aldosterone ◽  
The Relationship ◽  
Activator Inhibitor ◽  
Pai 1

Recent studies have defined a link between the renin-angiotensin-aldosterone system and fibrinolysis. The present study tests the hypothesis that endogenous aldosterone regulates plasminogen activator inhibitor-1 (PAI-1) production in humans. Hemodynamic parameters, PAI-1 and tissue-type plasminogen activator (t-PA) antigen, potassium, PRA, angiotensin II, and aldosterone were measured in nine male hypertensive subjects after a 3-wk washout, after 2 wk of hydrochlorothiazide (HCTZ; 25 mg plus 20 mmol KCl/d), and after 2 wk of spironolactone (100 mg/d plus KCl placebo). Spironolactone (P = 0.04), but not HCTZ (P = 0.57 vs. baseline; P = 0.1 vs. spironolactone), significantly lowered systolic blood pressure. Angiotensin II increased from baseline during both HCTZ (P = 0.02) and spironolactone (P = 0.02 vs. baseline; P = 0.19 vs. HCTZ) treatments. Although both HCTZ (P = 0.004) and spironolactone (P < 0.001 vs. baseline) increased aldosterone, the effect was greater with spironolactone (P < 0.001 vs. HCTZ). HCTZ increased PAI-1 antigen (P = 0.02), but did not alter t-PA antigen. In contrast, there was no effect of spironolactone on PAI-1 antigen (P = 0.28), whereas t-PA antigen was increased (P = 0.01). There was a significant correlation between PAI-1 antigen and serum aldosterone during both baseline and HCTZ study days (r2 = 0.57; P = 0.0003); however, treatment with spironolactone abolished this correlation (r2 = 0.13; P = 0.33). This study provides evidence that endogenous aldosterone influences PAI-1 production in humans.

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