Rondeau E, He C J, Zacharias U, Sraer J D
INSERM U 64 et Association Claude Bernard, Hôpital Tenon, Paris, France.
Semin Thromb Hemost. 1996;22(2):135-8. doi: 10.1055/s-2007-999000.
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).
许多肾小球和血管性肾炎与肾脏内纤维蛋白的形成和沉积有关。诱导纤维蛋白形成的凝血酶，还通过功能性凝血酶受体的激活，对循环细胞和固有肾小球细胞产生多种细胞效应。通过免疫组织化学和原位杂交，我们证明了功能性凝血酶受体在正常人类肾脏中的组成性表达。培养的肾小球上皮细胞和系膜细胞也表达功能性凝血酶受体，这通过针对该受体的特异性单克隆抗体结合和Northern印迹分析得以显示。凝血酶对培养的肾小球细胞具有强大的促有丝分裂作用，表明它至少在一定程度上可能是诱导肾小球疾病中肾小球细胞增殖的介质之一。此外，我们证明凝血酶上调这些细胞中纤溶酶原激活剂及其1型抑制剂的合成。凝血酶诱导这些细胞中的蛋白激酶C激活和细胞内钙增加。最后，我们证明在添加凝血酶和凝血酶受体激活肽后（同源内化）以及在添加佛波醇肉豆蔻酸酯后（异源内化），功能性凝血酶受体会内化。
