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Blood, 15 August 2004, Vol. 104, No. 4, pp. 1025-1033.
Prepublished online as a Blood First Edition Paper on May 4, 2004; DOI 10.1182/blood-2003-09-3334.
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Submitted October 2, 2003
Accepted March 23, 2004
Syndecan-1 upregulated by ephrinB2/EphB4 plays dual roles in inflammatory angiogenesis
Kuo Yuan, Tse-Ming Hong, Jeremy Chen, Wan-Hua Tsai, and Ming T Lin*
Periodontics Division, Department of Dentistry, National Cheng Kung University Hospital, Tainan City, Taiwan; Department of Biochemistry and Institute of Basic Medical Sciences, Medical School, National Cheng Kung University, Tainan City, Taiwan
School of Pharmacy, Natinal Taiwan University College of Medicine, Taipei City, Taiwan
Institute of Biomedical Sciences and Molecular Biology, National Chung Hsing University, Taichung, Taiwan
Department of Biochemistry and Institute of Basic Medical Sciences, Medical School, National Cheng Kung University, Tainan City, Taiwan
* Corresponding author; email: Lin1223{at}mail.ncku.edu.tw.
EphrinB2 and EphB4, its cognate receptor, are important in the vascular development of the mouse embryo. Their roles in human inflammatory angiogenesis, however, are not well understood. By examining hyper-inflammatory lesions, we saw that ephrinB2 was predominantly expressed in macrophage-like cells, and EphB4, in small venules. Because macrophages usually transmigrate through post-capillary venules during inflammation, we wanted to explore the downstream effects of EphB4 after binding to ephrinB2. By using cDNA microarray technique and following RT-PCR, we found that syntenin and syndecan-1 were up-regulated in EphB4+ endothelial cells dose- and time-dependently after stimulation with pre-clustered ephrinB2. In vitro, ephrinB2 suppressed the angiogenic effects of bFGF on EphB4+ endothelial cells, partially due to syndecan-1's competition with FGFR for bFGF. However, ephrinB2 exhibited angiogenic effects in vivo, possibly due to an inflammation-associated enzyme-heparanase. The enzymes could convert the inhibitory effect of ephrinB2 on EphB4+ endothelial cells to an activating effect by removing poorly sulfated side chains of upregulated syndecan-1 ectodomain. Depending on the presence of heparanases, the roles of syndecan-1 may be opposite in different physiological settings.

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