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World J Biol Chem. Oct 26, 2010; 1(10): 298-306
Published online Oct 26, 2010. doi: 10.4331/wjbc.v1.i10.298
Roles of sphingosine-1-phosphate signaling in angiogenesis
Yoh Takuwa, Wa Du, Xun Qi, Yasuo Okamoto, Noriko Takuwa, Kazuaki Yoshioka
Yoh Takuwa, Wa Du, Xun Qi, Yasuo Okamoto, Noriko Takuwa, Kazuaki Yoshioka, Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan
Noriko Takuwa, Department of Health and Medical Sciences, Ishikawa Prefectural Nursing University, 7-1 Nakanuma-tu, Kahoku, Ishikawa 929-1212, Japan
Author contributions: Takuwa Y wrote the paper, Du W, Qi X, Okamoto Y, Takuwa N and Yoshioka K edited the manuscript.
Supported by Grants from the Ministry of Education, Science, Sports and Culture of Japan and the Japan Society for the Promotion of Science, and the Practical Application Research program of Japan Science and Technology Agency Innovation plaza Ishikawa
Correspondence to: Yoh Takuwa, MD, PhD, Professor, Department of Physiology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan. ytakuwa@med.kanazawa-u.ac.jp
Telephone: +81-76-2652165 Fax: +81-76-2344223
Received: July 20, 2010
Revised: September 15, 2010
Accepted: September 22, 2010
Published online: October 26, 2010
Abstract

Sphingosine-1-phosphate (S1P) is a blood-borne lipid mediator with pleiotropic biological activities. S1P acts via the specific cell surface G-protein-coupled receptors, S1P1-5. S1P1 and S1P2 were originally identified from vascular endothelial cells (ECs) and smooth muscle cells, respectively. Emerging evidence shows that S1P plays crucial roles in the regulation of vascular functions, including vascular formation, barrier protection and vascular tone via S1P1, S1P2 and S1P3. In particular, S1P regulates vascular formation through multiple mechanisms; S1P exerts both positive and negative effects on angiogenesis and vascular maturation. The positive and negative effects of S1P are mediated by S1P1 and S1P2, respectively. These effects of S1P1 and S1P2 are probably mediated by the S1P receptors expressed in multiple cell types including ECs and bone-marrow-derived cells. The receptor-subtype-specific, distinct effects of S1P favor the development of novel therapeutic tactics for antitumor angiogenesis in cancer and therapeutic angiogenesis in ischemic diseases.

Keywords: Sphingosine-1-phosphate, Angiogenesis, Angiogenic therapy, Rac, Akt, Vascular maturation, Endothelial cells, Bone-marrow-derived cells