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Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCbeta2 axis.

 Yong-Sun Maeng  ;  Hyun-Jung Choi  ;  Ja-Young Kwon  ;  Yong-Won Park  ;  Kyu-Sil Choi  ;  Jeong-Ki Min  ;  Yun-Hee Kim  ;  Pann-Ghill Suh  ;  Kyung-Sun Kang  ;  Moo-Ho Won  ;  Young-Myeong Kim  ;  Young-Guen Kwon 
 BLOOD, Vol.113(1) : 233-243, 2009 
Journal Title
Issue Date
Animals ; Calcium/metabolism ; Cell Adhesion/physiology ; Cell Line, Tumor ; Cell Movement/physiology ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Fetal Blood/cytology ; GTP-Binding Protein alpha Subunits, Gi-Go/antagonists & inhibitors ; GTP-Binding Protein alpha Subunits, Gi-Go/metabolism ; Hematopoietic Stem Cells/cytology* ; Hematopoietic Stem Cells/metabolism ; Hindlimb/blood supply ; Humans ; Hypoxia/metabolism* ; Insulin-Like Growth Factor II/metabolism* ; Ischemia/metabolism* ; Male ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred C57BL ; Neovascularization, Physiologic/physiology ; Phospholipase C beta/genetics ; Phospholipase C beta/metabolism* ; RNA, Small Interfering ; Receptor, IGF Type 2/metabolism* ; Signal Transduction/physiology ; Umbilical Veins/cytology
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.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Ja Young(권자영) ORCID logo https://orcid.org/0000-0003-3009-6325
Park, Yong Won(박용원)
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