Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody

Cited 11 time in scopus
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Title
Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody
Author(s)
Byngtae Hwang; Sang Hyun Lee; Jang Seong Kim; ji Hyun Moon; I C Jeung; Na Geum Lee; Jongjin Park; H J Hong; Young Lai Cho; Haiyoung JungYoung-Jun ParkSeon-Jin LeeHee Gu LeeWon Kon KimBaek Soo HanKwang-Hee Bae; S J Chung; Y G Kwon; Sang Chul LeeSang Jick KimJeong Ki Min
Bibliographic Citation
Biomaterials, vol. 51, pp. 119-128
Publication Year
2015
Abstract
Angiopoietin-1 (Ang1) and its endothelium-specific receptor, tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2), play critical roles in vascular development. Although the Ang1/Tie2 system has been considered a promising target for therapeutic neovascularization, several imitations of large-scale production have hampered the development of recombinant Ang1 for therapeutics. In this study, we produced a fully human agonistic antibody against Tie2, designated 1-4h, and tested the applicability of 1-4h as an alternative to native Ang1 in therapeutic angiogenesis. 1-4h significantly enhanced the phosphorylation of Tie2 in a dose- and time-dependent manner in human Tie2-expressing HEK293 cells and human umbilical vein endothelial cells. Moreover, 1-4h induced the activation of Tie2-mediated intracellular signaling such as AKT, eNOS, MAPK, and Focal Adhesion Kinase p125FAK. In addition, 1-4h increased the chemotactic motility and capillary-like tube formation of endothelial cells invitro and enhanced the survival of serum-deprived endothelial cells. Taken together, our data clearly suggest that a human Tie2 agonistic antibody is a potentially useful therapeutic approach for the treatment of several ischemic diseases including delayed-wound healing and ischemic heart and limb diseases.
Keyword
Agonistic antibodyAngiogenesisAngiopoietin-1Tie2 receptor
ISSN
0142-9612
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.biomaterials.2015.01.062
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Research on National Challenges > Biodefense Research Center > 1. Journal Articles
Division of Biomaterials Research > Synthetic Biology and Bioengineering Research Center > 1. Journal Articles
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