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.
|Number of pages||10|
|Publication status||Published - 2015 May 1|
Bibliographical noteFunding Information:
This study was supported by the National Research Foundation of Korea , which was funded by the Ministry of Science, Information & Communication Technology and Future Planning (grants NRF-2012M3A9C6050331 , NRF-2012M3A9C7050101 , and NRF-2014M3A9C4066458 ), and by the Creative Allied Project (CAP) through the National Research Council of Science and Technology (NST).
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials