Figure 3: Tissue Factor (TF) contributes to pathogenesis of DN (hypothesis). A decrease in eNOS/NO, high fat diet and diabetes all stimulate TF expression. Increased TF expression in the kidney (observed in monocytes/ macrophages in glomerular mesangial area) activates the coagulation cascade, leading to the production of FVIIa, FXa and thrombin. These proteases can activate protease-activated receptors, which may enhance DN, inflammation and recruit monocyte/macrophages. Hypercoagulability and inflammation together likely make a vicious circle and exacerbate DN.