%0 Journal Article
%T The role of thrombomodulin lectin-like domain in inflammation
%A Yi-Heng Li
%A Cheng-Hsiang Kuo
%A Guey-Yueh Shi
%A Hua-Lin Wu
%J Journal of Biomedical Science
%D 2012
%I BioMed Central
%R 10.1186/1423-0127-19-34
%X Thrombomodulin (TM) is a cell surface-expressed transmembrane glycoprotein which is originally identified on vascular endothelium. The cDNA sequence of TM has been determined with the cloning and sequencing of the human TM gene [1]. The mature human TM protein and its secondary structure have also been resolved [2]. TM protein has 557 amino acids, and its structure consists of 5 domains including a highly charged N-terminal lectin-like domain (D1), a domain with six epidermal growth factor (EGF)-like structures (D2), a serine and threonine-rich domain (D3), a transmembrane domain (D4) and a cytoplasmic domain (D5) [2] (Figure 1). TM on vascular endothelial cells is an important molecule in human natural anticoagulation system. After a stimulus, blood coagulation cascade amplifies and produces a high level of thrombin, the key effector of coagulation cascade. Natural anticoagulant mechanisms are activated to prevent excessive thrombin generation. TM acts as a thrombin receptor on the surface of vascular endothelial cells. The binding of TM to thrombin significantly decreases the thrombin's effect in conversion of fibrinogen to fibrin, and activation of coagulation factor V, VIII and platelet. Thrombin-TM complex catalyzes the activation of protein C about 1000 times faster than free thrombin. Activated protein C proteolytically inactivates the coagulation cofactor Va and VIIIa, thereby inhibiting the amplification of the coagulation system [3-5]. The importance of TM in natural anticoagulant system was demonstrated by the observation that transgenic mice with endothelium-specific loss of TM developed severe spontaneous thrombosis in the arterial and venous circulation, and inevitably led to the death of animal [6]. In addition to endothelium, TM is expressed in smooth muscle cell [7], platelet [8], monocyte [9], and cardiomyocyte [10]. TM is also expressed in some cancer cells and influences the growth and metastasis of cancer [11,12]. The presence of TM in these cel
%K Thrombomodulin
%K Lectin
%K Inflammation
%U http://www.jbiomedsci.com/content/19/1/34