J. Biochem, 1999, Vol. 126, No. 1 137-145
© 1999 Japanese Biochemical Society
research-article |
Connective Tissue Growth Factor Induces the Proliferation, Migration, and Tube Formation of Vascular Endothelial Cells In Vitro, and Angiogenesis In Vivo1
,2
,3
*Department of Biochemistry and Molecular Dentistry, Okayama University Dental School Okayama 700-8525
Department of Biodental Research Center, Okayama University Dental School Okayama 700-8525
Department of Oral and Maxillofacial Surgery II, Okayama University Dental School Okayama 700-8525
Department of Fixed Prosthodontics, Okayama University Dental School Okayama 700-8525
¶Pharmaceutical Frontier Research Laboratories, Japan Tobacco Inc. Yokohama 236-0004
*Department of Oral Anatomy, Osaka University Faculty of Dentistry Suita, Osaka 565-0871
3To whom correspondence should be addressed. Tel: +81-86-235-6645, Fax: +81-86-235-6649, E-mail: takigawa6dent.okayama-u.ac.jp
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 oligonu-cleotide and antisense RNA suppresses the proliferation and migration of vascular endo-thelial 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.
2On leave of absence from the Department of Periodontology and Endodontology II, Okayama University Dental School
1This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and grants from the Sagawa Cancer Research Foundation, the Natio Foundation, and the Foundation for Growth Science in Japan.
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