The endothelial thrombomodulin system protects against diabetic nephropathy through two independent mechanisms: role of the lectin-like domain

Objective: The thrombomodulin (TM) protein C (PC) system is an endothelial dependent, cytoprotective system which has been initially identified based on its anticoagulant function. Following binding and inactivation of thrombin the complex of TM and thrombin activates PC via its EGF-domains 4–6. Activated PC (APC) has anticoagulant as well as cytoprotective properties. In addition TM mediates a direct cytoprotective effect through its lectin-like domain (LD), potentially via scavenging of HMGB-1 and thus preventing excess binding and activation of the receptor RAGE. The role of this endothelial system for diabet…