THROMBIN STIMULATION OF RENAL-CELLS

Numerous glomerular and vascular nephritides are associated with fibri n formation and deposition within the kidney, Thrombin, which induces fibrin formation, also exerts numerous cellular effects on both circul ating cells and intrinsic glomerular cells through the activation of t he functional thrombin receptor, By immunohistochemistry and in situ h ybridization, we demonstrated the constitutive expression of the funct ional thrombin receptor in the normal human kidney, Both glomerular ep ithelial and mesangial cells in culture also express the functional th rombin receptor, as shown by the binding of a specific monoclonal anti body against this receptor and Northern blot analysis, Thrombin has a potent mitogenic effect on cultured glomerular cells, suggesting that it could be at least, in part, one of the mediators that induces glome rular cell proliferation in glomerular diseases, Furthermore, we demon strated that thrombin upregulates the synthesis of plasminogen activat ors and their type 1 inhibitor in these cells, Thrombin induces protei n kinase C activation and an increase in intracellular calcium in thes e cells, Finally, we demonstrated that the functional thrombin recepto r is internalized after addition of thrombin and thrombin receptor-act ivating peptide (homologous internalization) and also after phorbol my ristate acetate addition (heterologous internalization).