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

Byungtae Hwang, Sang Hyun Lee, Jang Seong Kim, Ji Hyun Moon, In Cheul Jeung, Na Geum Lee, Jongjin Park, Hyo Jeong Hong, Young Lai Cho, Haiyoung Jung, Young Jun Park, Seon Jin Lee, Hee Gu Lee, Won Kon Kim, Baek Soo Han, Kwang Hee Bae, Sang J. Chung, Young Guen Kwon, Sang Chul Lee, Sang Jik KimJeong Ki Min

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)119-128
Number of pages10
Publication statusPublished - 2015 May 1

Bibliographical note

Funding 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).

Publisher Copyright:
© 2015 Elsevier Ltd.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials


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