Thrombin stimulation of renal cells

Abstract

Numerous glomerular and vascular nephritides are associated with fibrin formation and deposition within the kidney. Thrombin, which induces fibrin formation, also exerts numerous cellular effects on both circulating cells and intrinsic glomerular cells through the activation of the functional thrombin receptor. By immunohistochemistry and in situ hybridization, we demonstrated the constitutive expression of the functional thrombin receptor in the normal human kidney. Both glomerular epithelial and mesangial cells in culture also express the functional thrombin receptor, as shown by the binding of a specific monoclonal antibody 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 glomerular cell proliferation in glomerular diseases. Furthermore, we demonstrated that thrombin upregulates the synthesis of plasminogen activators and their type 1 inhibitor in these cells. Thrombin induces protein kinase C activation and an increase in intracellular calcium in these cells. Finally, we demonstrated that the functional thrombin receptor is internalized after addition of thrombin and thrombin receptor-activating peptide (homologous internalization) and also after phorbol myristate acetate addition (heterologous internalization).