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Title 

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

Authors 

Byngtae HwangSang Hyun LeeJang Seong Kimji Hyun MoonI C JeungNa Geum LeeJongjin ParkH J HongYoung Lai ChoHaiyoung JungYoung-Jun ParkSeon-Jin LeeHee Gu LeeWon Kon KimBaek Soo HanKwang-Hee BaeS J ChungY G KwonSang Chul LeeSang Jick KimJeong Ki Min

Publisher 

Elsevier

Issue Date 

2015

Citation 

Biomaterials, vol. 51, no. 0, pp. 119-128

Keywords 

Agonistic antibodyAngiogenesisAngiopoietin-1Tie2 receptor

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.

ISSN 

0142-9612

Link 

http://dx.doi.org/10.1016/j.biomaterials.2015.01.062

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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