Urokinase synthesis and binding by glomerular epithelial cells in culture

E. Rondeau, S. Ochi, R. Lacave, C. J. He, R. Medcalf, F. Delarue, J. D. Sraer

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Fibrin deposits are frequently observed in the course of proliferative extracapillary glomerulonephritis and could be related to a defective local fibrinolysis. We studied human glomerular epithelial cells in culture which were found to release mainly a urokinase-type plasminogen activator (u-PA) identified on zymography by its molecular weight (53 kD), its plasminogen activator activity, and its neutralization by specific polyclonal anti-u-PA IgG. Trace amounts of tissue-type plasminogen activator (t-PA) complexed to a plasminogen activator inhibitor type 1 (PA-1) were identified with specific antibodies. Specific binding sites were found at the surface of glomerular epithelial cells (kD: 2.10-9 M), partially occupied by secreted u-PA. The spontaneous u-PA activity of the culture medium conditioned by glomerular epithelial cells was very low, suggesting that u-PA was released in its inactive single chain proenzyme form (SC-u-PA). After activation of SC-u-PA by plasmin, u-PA activity of the culture medium was found to increase in a time- and dose-dependent manner when cells were incubated with phorbol myristic acetate (PMA). This effect was inhibited by H7, a protein kinase C inhibitor. Stimulation of u-PA synthesis by PMA was also observed in two different epithelial tubular cell lines, LLC-PK1 and MDCK cells. However, 8 bromo cyclic AMP which increased u-PA release by LLC-PK1 cells was found to inhibit u-PA release by PMA-stimulated glomerular epithelial cells and MDCK cells. By Northern blot analysis we found that PMA induced an increase of u-PA mRNA level in glomerular epithelial cells and that cyclic AMP had an opposite effect. Thus the fibrinolytic activity could be regulated by hormones and local mediators which activate these intracellular pathways.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalKidney International
Issue number4
Publication statusPublished - 1 Jan 1989
Externally publishedYes

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