title: Soluble THSD7A is an N-glycoprotein that promotes endothelial cell migration and tube formation in angiogenesis.
abstract: BACKGROUND
  Thrombospondin type I domain containing 7A (THSD7A) is a novel neural protein that is known to affect endothelial migration and vascular patterning during development. To further understand the role of THSD7A in angiogenesis, we investigated the post-translational modification scheme of THS7DA and to reveal the underlying mechanisms by which this protein regulates blood vessel growth.
  
  
  RESULTS
  Full-length THSD7A was overexpressed in human embryonic kidney 293T (HEK293T) cells and was found to be membrane associated and N-glycosylated. The soluble form of THSD7A, which is released into the cultured medium, was harvested for further angiogenic assays. We found that soluble THSD7A promotes human umbilical vein endothelial cell (HUVEC) migration and tube formation. HUVEC sprouts and zebrafish subintestinal vessel (SIV) angiogenic assays further revealed that soluble THSD7A increases the number of branching points of new vessels. Interestingly, we found that soluble THSD7A increased the formation of filopodia in HUVEC. The distribution patterns of vinculin and phosphorylated focal adhesion kinase (FAK) were also affected, which implies a role for THSD7A in focal adhesion assembly. Moreover, soluble THSD7A increased FAK phosphorylation in HUVEC, suggesting that THSD7A is involved in regulating cytoskeleton reorganization.
  
  
  CONCLUSIONS
  Taken together, our results indicate that THSD7A is a membrane-associated N-glycoprotein with a soluble form. Soluble THSD7A promotes endothelial cell migration during angiogenesis via a FAK-dependent mechanism and thus may be a novel neuroangiogenic factor.
authors.affiliation: Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Meng-Wei
authors.initials: MW
authors.lastname: Kuo
authors.forename: Chian-Huei
authors.initials: CH
authors.lastname: Wang
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Wu
authors.forename: Shing-Jyh
authors.initials: SJ
authors.lastname: Chang
authors.forename: Yung-Jen
authors.initials: YJ
authors.lastname: Chuang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012995:Solubility / Q000187:drug effects; D019699:Thrombospondins / Q000737:chemistry / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D006023:Glycoproteins; C546399:THSD7A protein, human; D019699:Thrombospondins; D051416:Focal Adhesion Protein-Tyrosine Kinases