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 Kim; Jeong Ki Min

doi:10.1016/j.biomaterials.2015.01.062

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 journal › Article › peer-review

12 Citations (Scopus)

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 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 language	English
Pages (from-to)	119-128
Number of pages	10
Journal	Biomaterials
Volume	51
DOIs	https://doi.org/10.1016/j.biomaterials.2015.01.062
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.biomaterials.2015.01.062

Cite this

Hwang, B., Lee, S. H., Kim, J. S., Moon, J. H., Jeung, I. C., Lee, N. G., Park, J., Hong, H. J., Cho, Y. L., Jung, H., Park, Y. J., Lee, S. J., Lee, H. G., Kim, W. K., Han, B. S., Bae, K. H., Chung, S. J., Kwon, Y. G., Lee, S. C., ... Min, J. K. (2015). Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody. Biomaterials, 51, 119-128. https://doi.org/10.1016/j.biomaterials.2015.01.062

@article{3632a935e15a4785aff60fc01fc6b567,

title = "Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody",

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.",

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

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: {\textcopyright} 2015 Elsevier Ltd.",

year = "2015",

month = may,

day = "1",

doi = "10.1016/j.biomaterials.2015.01.062",

language = "English",

volume = "51",

pages = "119--128",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

}

Hwang, B, Lee, SH, Kim, JS, Moon, JH, Jeung, IC, Lee, NG, Park, J, Hong, HJ, Cho, YL, Jung, H, Park, YJ, Lee, SJ, Lee, HG, Kim, WK, Han, BS, Bae, KH, Chung, SJ, Kwon, YG, Lee, SC, Kim, SJ & Min, JK 2015, 'Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody', Biomaterials, vol. 51, pp. 119-128. https://doi.org/10.1016/j.biomaterials.2015.01.062

TY - JOUR

T1 - Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody

AU - Hwang, Byungtae

AU - Lee, Sang Hyun

AU - Kim, Jang Seong

AU - Moon, Ji Hyun

AU - Jeung, In Cheul

AU - Lee, Na Geum

AU - Park, Jongjin

AU - Hong, Hyo Jeong

AU - Cho, Young Lai

AU - Jung, Haiyoung

AU - Park, Young Jun

AU - Lee, Seon Jin

AU - Lee, Hee Gu

AU - Kim, Won Kon

AU - Han, Baek Soo

AU - Bae, Kwang Hee

AU - Chung, Sang J.

AU - Kwon, Young Guen

AU - Lee, Sang Chul

AU - Kim, Sang Jik

AU - Min, Jeong Ki

N1 - 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.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84924857129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924857129&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2015.01.062

DO - 10.1016/j.biomaterials.2015.01.062

M3 - Article

C2 - 25771003

AN - SCOPUS:84924857129

SN - 0142-9612

VL - 51

SP - 119

EP - 128

JO - Biomaterials

JF - Biomaterials

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this