Syndecan（SDC）是細胞表面上的一種蛋白多醣，含有大量的硫酸乙醯肝素（heparan sulfate），SDC主要的功能是作為輔助受器，利用硫酸乙醯肝素和許多分子結合並協助這些分子和受器結合，像是一些生長因子、細胞外基質或是其他膜蛋白。目前在脊椎動物中發現四種SDC，分別為SDC-1到SDC-4。凝血酶調節素（thrombomodulin, TM）最早在血管內皮細胞被發現，是為人所熟知的抗凝血因子。在先前的研究中發現TM的類上皮生長因子區域（EGF-like domain, TMD23）具有促進血管新生功能；另外，也發現TM可以調節細胞的黏著。然而，TMD23以及TM是如何作用的還未充分了解。本實驗用穩定表現SDC的細胞來探討TMD23的作用是否利用SDC作為輔助受器。我們發現TMD23可以和肝素結合，並且在TMD23刺激之下，表現SDC的細胞生長速率比控制組快，其中又以穩定表現SDC-4的細胞變化最明顯；而利用共同免疫沉澱方法證實TMD23可以和SDC-4結合但不能和SDC-1結合。另一方面，由於TM可以當作是細胞黏著因子，我們也探討在細胞黏著以及移行時，SDC與TM之間的關係。同時表現TM及SDC在A2058細胞中，發現在細胞黏著於纖維黏蛋白（fibronectin）時，TM和SDC會共同表現在細胞的邊緣；而在HaCaT細胞移行時，TM則會和SDC-1結合。我們的結果顯示在細胞上SDC-4可作為TMD23的輔助受器，此外，在細胞進行黏著或移行時，細胞膜上的TM也會和膜上的SDC在一起作用，可能與調控細胞與細胞外基質的結合有關。

Syndecans (SDCs) are a family of cell surface heparan sulfate proteoglycans. Heparan sulfate side chains of syndecans bind to extracellular matrix and heparin-binding growth factors to present them to their receptors. Syndecans can also bind to other molecules on the cell surface such as integrins and selectins. Thus, syndecans are able to regulate cell spreading, adhesion, migration and proliferation because of these interactions. There are four syndecans that have been characterized in vertebrates: SDC-1, -2, -3, and -4. Thrombomodulin (TM), an anticoagulant membrane glycoprotein, is present mainly in endothelial cells, lung epithelial cells, and keratinocytes. In our previous study, we found that TM could mediate cell adhesion, and recombinant soluble human TM EGF-like domain protein (TMD23) could promote cell proliferation, migration, and angiogenesis. However, the mechanisms of TM and TMD23 functions still remained to be investigated. Since SDCs serve as co-receptors for various growth factors, we hypothesized that SDCs may play a role in modulating the function of TMD23 as a growth factor. On the other hand, since TM is an adhesion molecule, we investigated the relationship of SDCs and TM in cell spreading and migration. In the present study, we found that TMD23 could bind to immobilized heparin. HEK293 cells over-expressed SDCs proliferated more rapidly then control cells after TMD23 stimulation. Besides, we demonstrated that SDC-4 rather than SDC-1 co-immunoprecipitated with soluble TMD23. In A2058 cells which were co-transfection of full-length TM and SDCs cDNA, we also showed that TM co-localized with SDCs during cell spreading. The association of TM with SDC-1 was found in migrating HaCaT cells. These results suggested that TMD23 may use SDC-4 as its co-receptor through binding to the heparan sulfate side chains of SDC-4. During cell spreading and migration, TM in cooperation with SDCs regulated the interaction of cell and extracellular matrix.

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