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

Biomaterials
Byungtae HwangJeong-Ki Min

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 p125(FAK). In addition, 1-4h increased the chemotactic motility and capillary-like tube formation of endothelial cells in vitro 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 ischemi...Continue Reading

References

Jun 15, 1992·Biochemical and Biophysical Research Communications·J O ChlebounT V Chirila
Jul 1, 1997·Trends in Biochemical Sciences·F BussolinoG Persico
Sep 15, 1998·The Journal of Surgical Research·J StarkP Friedmann
Nov 11, 1998·Journal of Vascular Surgery·R L BushD N Pearson
Oct 12, 2000·The Journal of Surgical Research·R BaffourP Friedmann
Dec 7, 2002·Nature Structural Biology·Samuel DavisGeorge D Yancopoulos
Jun 5, 2003·Nature Medicine·Seppo Ylä-Herttuala, Kari Alitalo
Apr 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
Apr 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
Dec 16, 2005·Nature·Napoleone Ferrara, Robert S Kerbel
Mar 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chung-Hyun ChoGou Young Koh
May 5, 2011·The Journal of Clinical Investigation·Jeong-Ki MinYoung-Guen Kwon

❮ Previous
Next ❯

Citations

Jul 25, 2019·Chinese Medical Journal·Ling-Bing MengTao Gong
Nov 6, 2015·Frontiers in Physiology·Constanza E MartínezVerónica A Palma Alvarado
Jul 24, 2018·Molecular Pharmaceutics·Eyad IssaNicholas Pj Brindle
Sep 28, 2021·Drug Discovery Today·John S SchardtPeter M Tessier

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis