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Extracellular fragment of brain-specific angiogenesis inhibitor 1 suppresses endothelial cell proliferation by blocking αvβ5 integrin

Authors
 Jeong Tae Koh  ;  Hyun Kook  ;  Kyung Keun Kim  ;  Shin Jung  ;  Kyung Chul Yoon  ;  Mi-Young Kim  ;  Ji Hee Lee  ;  Byung Chul Jeong  ;  Young-Woo Seo  ;  Hae Jin Kee 
Citation
 EXPERIMENTAL CELL RESEARCH, Vol.294(1) : 172-184, 2004 
Journal Title
 EXPERIMENTAL CELL RESEARCH 
ISSN
 0014-4827 
Issue Date
2004
MeSH
Angiogenesis Inhibitors/chemistry ; Angiogenesis Inhibitors/metabolism ; Angiogenesis Inhibitors/pharmacology* ; Angiogenic Proteins/chemistry ; Angiogenic Proteins/metabolism ; Angiogenic Proteins/pharmacology* ; Apoptosis ; Brain/metabolism ; CD36 Antigens/immunology ; Caspase Inhibitors ; Cell Division/drug effects ; Cell Line ; Cells, Cultured ; Culture Media, Conditioned ; Cysteine Proteinase Inhibitors/pharmacology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/drug effects* ; Humans ; Integrin alphaV/immunology ; Integrins/analysis ; Integrins/antagonists & inhibitors* ; Integrins/physiology ; Necrosis ; Peptide Fragments/pharmacology ; Receptors, Vitronectin/analysis ; Receptors, Vitronectin/antagonists & inhibitors* ; Receptors, Vitronectin/physiology
Keywords
Brain-specific angiogenesis inhibitor 1 (BAI1) ; Neuron-specific gene ; Endothelial cells ; αvβ5 integrin ; Antiproliferative action
Abstract
Brain-specific angiogenesis inhibitor 1 (BAI1) is a transmembrane protein with anti-angiogenic activity. The mechanisms underlying BAI1 activity are unknown. In this study, we found that overexpression of BAI1 increased cell death in human umbilical vein endothelial cells (HUVECs) and, to a lesser degree, in SHSY5Y and U343 cells. Conditioned medium from BAI1-transfected U343 cells inhibited proliferation of HUVECs, and this effect was neutralized by addition of anti-BAI1 serum. The conditioned medium contained four cleavage products of the BAI1 extracellular domain. BAI1's middle extracellular region containing five thrombospondin type 1 repeats (BAI1-TSR) was sufficient for BAI1's antiproliferative effect on HUVECs. BAI1's action on HUVECs was blocked by anti-αv integrin, but not by anti-CD36 antibody treatment. Introduction of αvβ5 integrin into HEK293 cells rendered them susceptible to cell death by BAI1, and BAI1-TSR bound with αvβ5 integrin, but not to αvβ3 integrin in brain tissue. Fluorescent BAI1-TSR colocalized with αvβ5 integrin in HUVECs. Together, our results indicate that BAI1 has antiproliferative action on surrounding endothelial cells by blocking αvβ5 integrin, and its active region is BAI1-TSR. BAI1-TSR could be valuable for regulating brain angiogenesis.
Full Text
http://www.sciencedirect.com/science/article/pii/S0014482703006177
DOI
10.1016/j.yexcr.2003.11.008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111570
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