Effect of Endothelin 1 on Fibrinolysis and Plasminogen Activator Inhibitor 1 Synthesis in Rat Mesangial Cells

Nephron ◽  
1996 ◽  
Vol 73 (2) ◽  
pp. 273-279 ◽  
2008 ◽  
Vol 36 (05) ◽  
pp. 1005-1015 ◽  
Author(s):  
Jun Yuan ◽  
Xiaoqin Wang ◽  
Taohou Chen ◽  
Gang Chen ◽  
Yanfang Lu

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.


1996 ◽  
Vol 320 (3) ◽  
pp. 777-783 ◽  
Author(s):  
Nadia ABDEL WAHAB ◽  
Roger M. MASON

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.


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