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TGFBIp regulates differentiation of EPC (CD133(+) C-kit(+) Lin(-) cells) to EC through activation of the Notch signaling pathway.

 Yong-Sun Maeng  ;  Yeon Jeong Choi  ;  Eung Kweon Kim 
 STEM CELLS, Vol.33(6) : 2052-2062, 2015 
Journal Title
Issue Date
Cell Differentiation/physiology* ; Cell Movement/physiology* ; Cells, Cultured ; Endothelial Progenitor Cells/cytology* ; Endothelium, Vascular/cytology* ; Extracellular Matrix/metabolism ; Extracellular Matrix Proteins/metabolism* ; Humans ; Neovascularization, Physiologic/physiology ; Receptors, Notch/metabolism* ; Signal Transduction* ; Transforming Growth Factor beta/metabolism*
Differentiation ; EPC ; Notch ; TGFBIp
Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs recognize the extracellular matrix (ECM), migrate, differentiate, and undergo tube morphogenesis. The ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behavior. Here, we tested the importance of transforming growth factor-beta-induced protein (TGFBIp) in regulation of the differentiation and angiogenic potential of human cord blood-derived EPCs (CD133(+) C-kit(+) Lin(-) cells). EPCs displayed increased endothelial differentiation when plated on TGFBIp compared to fibronectin. EPCs also exhibited increased adhesion and migration upon TGFBIp stimulation. Moreover, TGFBIp induced phosphorylation of the intracellular signaling molecules SRC, FAK, AKT, JNK, and ERK in EPCs. Using integrin-neutralizing antibodies, we showed that the effects of TGFBIp on EPCs are mediated by integrins α4 and α5. Furthermore, TGFBIp increased the adhesion, migration, and tube formation of CD34(+) mouse bone marrow stem cells in vitro. Gene expression analysis of EPCs plated on TGFBIp revealed that EPCs stimulated by TGFBIp exhibit increased expression of Notch ligands, such as delta-like 1 (DLL1) and Jagged1 (JAG1), through nuclear factor-kappa B signaling activation. Collectively, our findings demonstrate, for the first time, that locally generated TGFBIp at either wounds or tumor sites may contribute to differentiation and angiogenic function of EPCs by augmenting the recruitment of EPCs and regulating the expression of endothelial genes DLL1 and JAG1.
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Appears in Collections:
5. Research Institutes (연구소) > Corneal Dystrophy Research Institute (각막이상증연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Maeng, Yong Sun(맹용선) ORCID logo https://orcid.org/0000-0003-1694-8405
Choi, Yeon Jeong(최연정)
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