[Mechanisms of thrombin induced proliferation and detachment of glomerular endothelial cells]

To clarify the mechanisms of thrombin contributing to the progression of glomerular diseases by injuring glomerular endothelial cells (GECs), we studied the effects of thrombin on GECs in vitro. Cell proliferation was detected with MTT incorporation, total plasminogen activator (PA) and tissue type PA (t-PA) activities were detected with fibrin plate and chromatogenic substrate methods and fibronectin was detected with ELISA as well as indirect immunofluore scence. 0.4-3.2 NIH U/ml thrombin promoted GEC proliferation significantly (P < 0.05). Thrombin promoted cell detachment, which can be inhibited by hirudin or aprotinin. Thrombin enhanced total PA and t-PA activities of GECs significantly (P < 0.01). Fibronectin in the supernatants of thrombin-stimulated GECs decreased significantly (P < 0.01) and in the extracellular compartment also decreased. The decrease was inhibited by hirudin and aprotinin. In conclusion, thrombin can induce GEC proliferation and GEC detachment. The latter is probably related to PA-mediated over-degradation of extracellular matrices such as fibronectin, which are needed for cell attachment.