Dataset Information

Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function.

ABSTRACT: Outgrowth endothelial cells (OECs) are a subpopulation of endothelial progenitor cells (EPCs) that have the capacity for proliferation and the ability to promote angiogenesis. In this study, we identified Nectin-2 as a surface protein of OECs through unbiased quantitative proteomics analysis. Using immunocytochemistry and flow cytometry, we confirmed that Nectin-2 is highly expressed on OECs. Nectin-2 (CD112) expression was limited or lower on mononuclear cells (MNCs) and mature tube-forming endothelial cells (ECs). Blocking Nectin-2 with a neutralizing monoclonal antibody significantly increased the trans-well migration and tube forming capacity of OECs. Similarly, Nectin-2 knockdown resulted in enhanced tube formation, cell migration and proliferation with p-Erk activation. Moreover, Nectin-2 deficiency resulted in compensatory increase of other Nectin family genes including Nectin-3 and Necl-4 which promote VEGFR signaling. These results indicate that Nectin-2 is a surface marker and an important regulator of OECs, with significant implications for the isolation of OECs and blocking Nectin-2 on OECs by an antibody for angiogenic applications.

SUBMITTER: Son Y

PROVIDER: S-EPMC5038973 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function.

Son YeonSung Y Lee BomNaeRin B Choi Young-Jin YJ Jeon Seon Ae SA Kim Ju-Hyun JH Lee Hoo-Keun HK Kwon Sang-Mo SM Cho Je-Yoel JY

PloS one 20160927 9

Outgrowth endothelial cells (OECs) are a subpopulation of endothelial progenitor cells (EPCs) that have the capacity for proliferation and the ability to promote angiogenesis. In this study, we identified Nectin-2 as a surface protein of OECs through unbiased quantitative proteomics analysis. Using immunocytochemistry and flow cytometry, we confirmed that Nectin-2 is highly expressed on OECs. Nectin-2 (CD112) expression was limited or lower on mononuclear cells (MNCs) and mature tube-forming end ...[more]

PMID: 27676263

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Project description:ObjectivesAutologous blood outgrowth endothelial cells (BOECs) have been proposed to induce therapeutic angiogenesis for treating cardiovascular diseases (CVDs). The aim of the present study was to investigate the proliferative potential and angiogenic characteristics of BOECs among middle-aged and older adults, the population particularly susceptible to CVDs.MethodsBOECs were isolated from 48 peripheral blood samples of subjects aged 56 ± 4 years. The cells were then distinguished based on their proliferative abilities, and their phenotype, tube formation capacity, and migratory activity were compared using immunofluorescence staining, flow cytometry, tube formation assay, and wound healing assay, respectively. Correlations between demographic, clinical, and dietary parameters with the number of BOECs were also assessed.ResultsA total of 132 BOEC colonies with different proliferative potentials were obtained, including colonies lost proliferative ability before passage 3 (named LPA), stopped proliferating during passage 3-8 (HPA (3-8)), and proliferated after passage 8 (HPA (> 8)). LPA cells appeared later and displayed abnormal morphology, while HPA (3-8) cells exhibited alterations in von Willebrand factor morphology and lower KDR expression. HPA (> 8) cells obtained higher branching intervals and individual cell migration velocity compared with those of HPA (3-8) cells. Correlation analysis showed that the number of both LPA and HPA colonies were positively associated with several CVD risk factors. Additionally, the number of LPA colonies was positively associated with servings of meats and alternatives, fruits, fruits and vegetables, as well as the protein intake.ConclusionsOur findings provide evidence that the middle-aged and older populations possess BOECs with different proliferative and angiogenic potentials, exhibiting distinctions in cell morphology, appearance dates, VWF morphology, and KDR expression. Strikingly, a higher number of BOECs is likely associated with an increased risk of CVDs, while the number of BOECs with low proliferative ability may be regulated by diet.

Dataset Information

Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function.

Publications

Nectin-2 (CD112) Is Expressed on Outgrowth Endothelial Cells and Regulates Cell Proliferation and Angiogenic Function.

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