Glomerular matrix accumulation is linked to inhibition of the plasmin protease system

Kidney Int. 1992 Dec;42(6):1462-9. doi: 10.1038/ki.1992.442.


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 anti-serum 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Glomerulonephritis / etiology
  • Glomerulonephritis / metabolism
  • Immunohistochemistry
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Plasminogen Activator Inhibitor 1 / biosynthesis*
  • Plasminogen Activators / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology


  • Plasminogen Activator Inhibitor 1
  • Platelet-Derived Growth Factor
  • Transforming Growth Factor beta
  • Plasminogen Activators