Monomeric CXCL12 outperforms its dimeric and wild type variants in the promotion of human endothelial progenitor cells' function

Shuang Chang; Yaning Li; Fang Yuan; Meijie Qu; Yaying Song; Zhijun Zhang; Guo-Yuan Yang; Yongting Wang

doi:10.1016/j.bbrc.2017.03.172

Monomeric CXCL12 outperforms its dimeric and wild type variants in the promotion of human endothelial progenitor cells' function

Biochem Biophys Res Commun. 2017 Jun 24;488(2):303-310. doi: 10.1016/j.bbrc.2017.03.172. Epub 2017 May 6.

Authors

Shuang Chang¹, Yaning Li², Fang Yuan¹, Meijie Qu³, Yaying Song⁴, Zhijun Zhang¹, Guo-Yuan Yang⁵, Yongting Wang⁶

Affiliations

¹ Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
² Department of Neurosurgery, Stanford University School of Medicine, MSLS Building, P306, 1201 Welch Road, Room P306, Stanford, CA 94305, USA.
³ Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
⁴ Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
⁵ Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: gyyang0626@163.com.
⁶ Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: ytwang@sjtu.edu.cn.

PMID: 28487111
DOI: 10.1016/j.bbrc.2017.03.172

Abstract

CXCL12 overexpression improves neurobehavioral recovery during post-ischemic stroke through multiple mechanisms including promoting endothelial progenitor cells function in animal models. It has been proposed that the monomer and dimer forms possess differential chemotactic and regulatory function. The aim of present study is to explore whether a monomeric or dimeric CXCL12 plays a different role in the endothelial progenitor cells proliferation, migration, and tube-formation in vitro. In this study, we transferred monomeric, dimeric and wild type CXCL12 gene into endothelial progenitor cells via lentiviral vectors. We investigated endothelial progenitor cells function following the interaction of CXCL12/CXCR4 or CXCL12/CXCR7 and downstream signaling pathways. Our results showed that the monomeric CXCL12 transfected endothelial progenitor cells had enhanced ability in cell proliferation, migration, and tube-formation compared to that in dimeric or wild type controls (p < 0.05). Both CXCR4 and CXCR7 were significantly overexpressed in the monomeric CXCL12 transfected endothelial progenitor cells compared to that in the dimeric or wide type controls (p < 0.05). The function of migration, but not proliferation or tube-formation, was significantly reduced in the monomeric CXCL12 transfected endothelial progenitor cells when the cells were pre-treated with either CXCR4 inhibitor AMD3100 or siCXCR7 (p < 0.05), suggesting this cell function was partially regulated by CXCL12/CXCR4 and CXCL12/CXCR7 signal pathways. Our study demonstrated that monomeric CXCL12 was the fundamental form, which played important roles in endothelial progenitor cells' proliferation, migration, and tube-formation.

Keywords: CXCL12; CXCR4; CXCR7; Endothelial progenitor cells; Monomer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Movement
Chemokine CXCL12 / chemistry*
Chemokine CXCL12 / genetics
Chemokine CXCL12 / metabolism*
Endothelial Progenitor Cells / cytology*
Endothelial Progenitor Cells / metabolism*
Humans

Substances

CXCL12 protein, human
Chemokine CXCL12