| | |  | | | | Record from Web of Science® | | | | | | |
| GLOMERULAR MATRIX ACCUMULATION IS LINKED TO INHIBITION OF THE PLASMIN PROTEASE SYSTEM |
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| Author(s): TOMOOKA S, BORDER WA, MARSHALL BC, NOBLE NA |
| Source: KIDNEY INTERNATIONAL Volume: 42 Issue: 6 Pages: 1462-1469 Published: DEC 1992 |
| Times Cited: 188 References: 35 |
| Abstract: TGF-beta plays a pivotal role in the pathological accumulation of extracellular matrix in experimental glomerulonephritis. Increased TGF-beta expression leads to increased synthesis and deposition of extracellular matrix components while administration of antiserum to TGF-beta suppresses the major manifestations of the disease. We hypothesized that TGF-beta might also enhance matrix accumulation by decreasing matrix turnover via effects on protease/protease inhibitor balance. Plasmin is a potent protease capable of degrading a variety of matrix molecules. Plasmin generation from plasminogen is regulated by plasminogen activator(s) (PA) and plasminogen activator inhibitor(s) (PAI). In this study PA activity was markedly reduced and PAI-1 synthesis dramatically increased when TGF-beta was added to normal glomeruli. Diseased glomeruli also showed decreased PA activity, increased PAI-1 synthesis and increased PAI-1 deposition into matrix. Administration of anti-TGF-beta serum to glomerulonephritic rats blocked the expected increase in glomerular PAI-1 deposition. Thus changes in the PA/PAI balance favoring accumulation of matrix are induced by TGF-beta in normal glomeruli and are present in nephritic glomeruli when endogenous TGF-beta production is high. Our findings implicate the plasmin protease system in tissue repair following acute glomerular injury and suggest another mechanism by which TGF-beta enhances the matrix accumulation characteristic of many glomerular diseases. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV UTAH, SCH MED, DEPT NEPHROL, SALT LAKE CITY, UT 84132 USA
2. UNIV UTAH, SCH MED, DEPT PULM MED, SALT LAKE CITY, UT 84112 USA |
| Publisher: BLACKWELL SCIENCE INC, 350 MAIN ST, MALDEN, MA 02148 |
| Subject Category: Urology & Nephrology |
| IDS Number: JY528 |
| ISSN: 0085-2538 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |