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Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLCβ2 axis
Maeng, Yong-Sun,Choi, Hyun-Jung,Kwon, Ja-Young,Park, Yong-Won,Choi, Kyu-Sil,Min, Jeong-Ki,Kim, Yun-Hee,Suh, Pann-Ghill,Kang, Kyung-Sun,Won, Moo-Ho,Kim, Young-Myeong,Kwon, Young-Guen American Society of Hematology 2009 Blood Vol.113 No.1
<B>Abstract</B><P>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 Ca2+ mobilization induced by the β2 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.</P>
Maeng, Yong-Sun,Kwon, Ja Young,Kim, Eung Kweon,Kwon, Young-Guen AlphaMed Press 2015 Stem Cells Vol.33 No.5
<P>As the ability to control the differentiation of endothelial stem/progenitor cells (EPCs) into vascular endothelial cell lineages could be useful for promoting neovascularization, it is important to obtain a deeper understanding of the epigenetic mechanisms that regulate EPC differentiation and neovascularization. Heterochromatin protein 1α (HP1α) is known to be involved in the epigenetic regulation of gene silencing. However, recent reports demonstrate that HP1α can also activate gene expression during cell differentiation. In this study, microarray analysis revealed that HP1α expression was induced during EPC differentiation and is associated with the expression of outgrowing endothelial cell (OEC)-specific protein markers. To explore the role of HP1α in the differentiation of EPCs to OECs, its expression was knocked-down or over-expressed in differentiating EPCs. Overexpression of HP1α promoted the differentiation and angiogenic activity of EPCs in vitro and in vivo, whereas knockdown of HP1α led to a defect in OEC migration, tube formation, and angiogenic sprouting activity. Gene expression profiling showed increased expression of angiogenic genes, including NOTCH1, cadherin-5, and angiopoietin-like-2, and decreased expression of progenitor cell marker genes, including CD133, CXCR4, and C-KIT, in HP1α-overexpressing EPCs. Also, increased HP1α at an early stage of EPC differentiation may regulate angiogenic gene transcription by interacting with chromatin that modifies epigenetic factors such as the methyl-CpG binding domain, Polycomb group ring finger 2, and DNA methyltransferases. Our findings demonstrate, for the first time, that HP1α plays an important role in the differentiation and angiogenic function of EPCs by regulating endothelial gene expression. Stem Cells 2015;33:1512-1522.</P>
Poster Session : IGF2/IGF2R system is a novel regulator of endothelial progenitor cell homing
( Yong Sun Maeng ),( Yeon Sook Choi ),( Seung Sik Rho ),( Ji Hye Kim ),( Yong Hak Kim ),( Jeong Ki Min ),( Ja Young Kwon ),( Yong Won Park ),( Young Myeong Kim ),( Young Guen Kwon ) 생화학분자생물학회 2006 생화학분자생물학회 춘계학술발표논문집 Vol.2006 No.-