Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo.
Connective tissue growth factor (CTGF) is a novel cysteine-rich, secreted protein. Recently, we found that inhibition of the endogenous expression of CTGF by its antisense oligonucleotide and antisense RNA suppresses the proliferation and migration of vascular endothelial cells. In the present study, the following observations demonstrated the angiogenic function of CTGF in vitro and in vivo: (i) purified recombinant CTGF (rCTGF) promoted the adhesion, proliferation and migration of vascular endothelial cells in a dose-dependent manner under serum-free conditions, and these effects were inhibited by anti-CTGF antibodies; (ii) rCTGF markedly induced the tube formation of vascular endothelial cells, and this effect was stronger than that of basic fibroblast growth factor or vascular endothelial growth factor; (iii) application of rCTGF to the chicken chorioallantoic membrane resulted in a gross angiogenic response, and this effect was also inhibited by anti-CTGF antibodies. (iv) rCTGF injected with collagen gel into the backs of mice induced strong angiogenesis in vivo. These findings indicate that CTGF is a novel, potent angiogenesis factor which functions in multi-stages in this process.
Shimo
T
T
Department of Biochemistry and Molecular Dentistry, Okayama University Dental School, Okayama, 700-8525, Japan.
Nakanishi
T
T
Nishida
T
T
Asano
M
M
Kanyama
M
M
Kuboki
T
T
Tamatani
T
T
Tezuka
K
K
Takemura
M
M
Matsumura
T
T
Takigawa
M
M
D000482:Allantois / Q000166:cytology / Q000187:drug effects; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000494:pharmacology; D055513:Connective Tissue Growth Factor; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D006133:Growth Substances / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D000906:Antibodies; C526318:CCN2 protein, mouse; C526316:CCN2 protein, rat; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D003094:Collagen