| Summary: | 碩士 === 國立成功大學 === 生物化學研究所 === 95 === Thrombomodulin (TM) is widely expressed in various cell types. Besides anti-coagulant activity, the well-known function of TM, it may have other important biological functions. The previous study showed that TM fragments are found in serum and urine. In this study, the extracellular TM domain was used to study its cellular functions. Human recombinant TMD23 domain (rhTMD23) containing six tandem epidermal growth factor-like (EGF-like) domains and Ser/Thr rich domain exhibits mitogenic activity and promote endothelial cell (EC) migration. The rhTMD23 could also promotes vascular smooth muscle cells (VSMC) migration. VSMCs are one of important members of aortic vessel and migrate to neointima crucial to the development of intimal thickening that characterizes various vascular diseases, including atherosclerosis. In vitro, rhTMD23 significantly induced redistribution of focal adhesion molecules to cell leading edge. FAK, JNK, paxillin and other focal adhesion protein are activated in rhTMD23-mediated pathways. In addition, rhTMD23 treatment could affect the mRNA expression and activity of matrix metalloproteases (MMPs); thus caused the protease cleave extracellular matrix (e.g., collagens, elastin, proteoglycans). Increased expression of MMPs plays an important role in the regulation of VSMCs migration and is involved in disease processes. Furthermore, we found that rhTMD23 could bind to avb3 integrin and increasing avb3 integrin expression on cell surface. This result suggests that avb3 integrin might midiate rhTMD23-induced VSMC migration.
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