Histidine-rich glycoprotein inhibited high mobility group box 1 in complex with heparin-induced angiogenesis in matrigel plug assay.
Histidine-rich glycoprotein (HRG) is a heparin-binding glycoprotein present in plasma at 100microg/ml. A recent study revealed that HRG suppressed heparin-dependent basic fibroblast growth factor (bFGF)-induced angiogenesis. Additionally, we reported that high mobility group box 1 (HMGB1) in complex with heparin induces angiogenesis; therefore, we examined the effect of HRG on heparin-dependent HMGB1-induced angiogenesis in the present study. HRG completely inhibited angiogenesis induced by HMGB1 in complex with heparin. HRG inhibited the diffusion of a complex of HMGB1 with heparin from matrigel into surrounding tissue. HRG also competed with HMGB1 for heparin binding in vitro. Moreover, HRG inhibited heparin-dependent vascular endothelial growth factor-A(165) (VEGF-A(165))-induced angiogenesis. These results strongly suggested that HRG might be an inhibitor of angiogenesis induced by growth factors with heparin binding activity and that HRG may be a potential drug for angiogenic diseases, including tumor growth.
Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Hidenori
H
Wake
Shuji
S
Mori
Keyue
K
Liu
Hideo K
HK
Takahashi
Masahiro
M
Nishibori
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001672:Biocompatible Materials; D003094:Collagen; D004338:Drug Combinations; D005786:Gene Expression Regulation / Q000187:drug effects; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D020007:Implants, Experimental; D007797:Laminin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000099053:Histidine-Rich Glycoprotein
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D001672:Biocompatible Materials; D004338:Drug Combinations; D024243:HMGB1 Protein; D007797:Laminin; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000099053:Histidine-Rich Glycoprotein; C059485:matrigel; D006493:Heparin; D003094:Collagen