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Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis

Menoud, P. A.
Fulpius, T.
Pastore, Y.
Takahashi, S.
Fossati-Jimack, Liliane
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Published in Kidney International. 1995, vol. 48, no. 5, p. 1459-1468
Abstract Three major components of the plasminogen activators (PA)/plasmin system are synthesized physiologically in glomeruli, and can be involved in glomerular proteolysis and extracellular matrix metabolism: tissue-type PA (tPA), urokinase (uPA) and PA inhibitor type 1 (PAI-1). To explore the possible role of a dysregulation of the plasmin protease system in the development and progression of lupus-like glomerulonephritis, we studied the expression of the renal plasmin protease components during the course of the disease, either acute, induced by IgG3 monoclonal cryoglobulins, or chronic, occurring spontaneously in three different lupus-prone mice: (NZBxNZW)F1, BXSB and MRL-lpr/lpr. RNase protection assays and in situ hybridizations revealed a marked glomerular induction of PAI-1 mRNA abundance without any significant changes in renal tPA and uPA mRNA levels in the two different types of lupus-like glomerulonephritis. The overexpression of PAI-1 mRNA occurred in parallel with a significant decrease in glomerular tPA-catalyzed enzymatic activity as determined by zymographic analysis. In addition, a concomitant increase in glomerular expression of transforming growth factor beta 1 (TGF-beta 1) mRNA was observed. The demonstration of a close correlation between the PAI-1 and TGF-beta 1 mRNA levels and the severity of lupus-like glomerular lesions suggests that a pertubation of the glomerular PA/PAI balance, resulting from a marked TGF-beta 1-mediated induction of PAI-1 gene expression, plays an important role in the progression of lupus-like glomerular lesions, leading to glomerulosclerosis.
Keywords AnimalsAntibodies, Monoclonal/immunology/pharmacologyChronic DiseaseCryoglobulins/immunologyImmunoglobulin G/immunologyKidney Glomerulus/metabolismLupus Nephritis/immunology/ metabolismMiceMice, Inbred BALB CMice, Inbred C57BLPlasminogen Activator Inhibitor 1/genetics/ metabolismRNA, Messenger/metabolismRheumatoid Factor/immunologyTissue DistributionTransforming Growth Factor beta/genetics
PMID: 8544402
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MOLL, Solange et al. Induction of plasminogen activator inhibitor type 1 in murine lupus-like glomerulonephritis. In: Kidney International, 1995, vol. 48, n° 5, p. 1459-1468. https://archive-ouverte.unige.ch/unige:8911

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Deposited on : 2010-07-12

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