title: Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCbeta2 axis.
abstract: Homing of endothelial progenitor cells (EPCs) to the neovascular zone is now considered to be an essential step in the formation of vascular networks during embryonic development and also for neovascularization in postnatal life. We report here the prominent role of the insulin-like growth factor 2 (IGF2)/IGF2 receptor (IGF2R) system in promoting EPC homing. With high-level expression of IGF2R in EPCs, IGF2-induced hypoxic conditions stimulated multiple steps of EPC homing in vitro and promoted both EPC recruitment and incorporation into the neovascular area, resulting in enhanced angiogenesis in vivo. Remarkably, all IGF2 actions were exerted predominantly through IGF2R-linked G(i) protein signaling and required intracellular Ca(2+) mobilization induced by the beta2 isoform of phospholipase C. Together, these findings indicate that locally generated IGF2 at either ischemic or tumor sites may contribute to postnatal vasculogenesis by augmenting the recruitment of EPCs. The utilization of the IGF2/IGF2R system may therefore be useful for the development of novel means to treat angiogenesis-dependent diseases.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Maeng
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Choi
authors.forename: Ja-Young
authors.initials: JY
authors.lastname: Kwon
authors.forename: Yong-Won
authors.initials: YW
authors.lastname: Park
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: C035170:IGF2 protein, human; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II; C518036:PLCB2 protein, human; D054799:Phospholipase C beta; D020780:Matrix Metalloproteinase 9; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D002118:Calcium