Thrombospondin type I domain containing 7A (THSD7A) mediates endothelial cell migration and tube formation.
Angiogenesis is a highly organized process controlled by a series of molecular events. While much effort has been devoted to identifying angiogenic factors and their reciprocal receptors, far less information is available on the molecular mechanisms underlying directed endothelial cell migration. To search for novel proteins that participate in this process, we used the serial analysis of gene expression (SAGE) transcript profiling approach to identify genes that are selectively expressed in endothelial cells (ECs). Two EC SAGE libraries were constructed from human umbilical vein and artery ECs to enable data-mining against other non-ECs. A novel endothelial protein, Thrombospondin Type I Domain Containing 7A (THSD7A), with preferential expression in placenta vasculature and in human umbilical vein endothelial cells (HUVECs) was identified and targeted for further characterization. Overexpression of a THSD7A carboxyl-terminal fragment in HUVECs inhibited cell migration and disrupted tube formation, while suppression of THSD7A expression enhanced HUVEC migration and tube formation. Immunohistological analysis revealed that THSD7A was expressed at the leading edge of migrating HUVECs, and it co-localized with alpha(V)beta(3) integrin and paxillin. This distribution was dispersed from focal adhesions after disruption of the actin cytoskeleton, suggesting the involvement of THSD7A in cytoskeletal organization. Our results show that THSD7A is a novel placenta endothelial protein that mediates EC migration and tube formation, and they highlight its potential as a new target for anti-angiogenic therapy.
Wang
Chieh-Huei
CH
Department of Life Science, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, 30013 Taiwan, ROC.
Su
Pei-Tsu
PT
Du
Xiao-Yan
XY
Kuo
Meng-Wei
MW
Lin
Chia-Yi
CY
Yang
Chung-Chi
CC
Chan
Hau-Shien
HS
Chang
Shing-Jyh
SJ
Kuo
Calvin
C
Seo
Kyunga
K
Leung
Lawrence L
LL
Chuang
Yung-Jen
YJ
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D057225:Data Mining; D042783:Endothelial Cells / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000235:genetics; D051419:Paxillin / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014469:Umbilical Arteries / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
D000199:Actins; D039302:Integrin alphaVbeta3; C496061:PXN protein, human; D051419:Paxillin; C546399:THSD7A protein, human; D019699:Thrombospondins