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      Androgen Modulates Functions of Endothelial Progenitor Cells through Activated Egr1 Signaling

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          Abstract

          Researches show that androgens have important effects on migration of endothelial cells and endothelial protection in coronary heart disease. Endothelial progenitor cells (EPCs) as a progenitor cell type that can differentiate into endothelial cells, have a critical role in angiogenesis and endothelial protection. The relationship between androgen and the functions of EPCs has animated much interest and controversy. In this study, we investigated the angiogenic and migratory functions of EPCs after treatment by dihydrotestosterone (DHT) and the molecular mechanisms as well. We found that DHT treatment enhanced the incorporation of EPCs into tubular structures formed by HUVECs and the migratory activity of EPCs in the transwell assay dose dependently. Moreover, microarray analysis was performed to explore how DHT changes the gene expression profiles of EPCs. We found 346 differentially expressed genes in androgen-treated EPCs. Angiogenesis-related genes like Egr-1, Vcan, Efnb2, and Cdk2ap1 were identified to be regulated upon DHT treatment. Furthermore, the enhanced angiogenic and migratory abilities of EPCs after DHT treatment were inhibited by Egr1-siRNA transfection. In conclusion, our findings suggest that DHT markedly enhances the vessel forming ability and migration capacity of EPCs. Egr1 signaling may be a possible pathway in this process.

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          Most cited references44

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            The Gene Ontology (GO) project in 2006

            (2005)
            The Gene Ontology (GO) project () develops and uses a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see ). The GO Consortium continues to improve to the vocabulary content, reflecting the impact of several novel mechanisms of incorporating community input. A growing number of model organism databases and genome annotation groups contribute annotation sets using GO terms to GO's public repository. Updates to the AmiGO browser have improved access to contributed genome annotations. As the GO project continues to grow, the use of the GO vocabularies is becoming more varied as well as more widespread. The GO project provides an ontological annotation system that enables biologists to infer knowledge from large amounts of data.
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              Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization.

              Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in human peripheral blood and shown to be incorporated into foci of neovascularization, consistent with postnatal vasculogenesis. We determined whether endogenous stimuli (tissue ischemia) and exogenous cytokine therapy (granulocyte macrophage-colony stimulating factor, GM-CSF) mobilize EPCs and thereby contribute to neovascularization of ischemic tissues. The development of regional ischemia in both mice and rabbits increased the frequency of circulating EPCs. In mice, the effect of ischemia-induced EPC mobilization was demonstrated by enhanced ocular neovascularization after cornea micropocket surgery in mice with hindlimb ischemia compared with that in non-ischemic control mice. In rabbits with hindlimb ischemia, circulating EPCs were further augmented after pretreatment with GM-CSF, with a corresponding improvement in hindlimb neovascularization. There was direct evidence that EPCs that contributed to enhanced corneal neovascularization were specifically mobilized from the bone marrow in response to ischemia and GM-CSF in mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. These findings indicate that circulating EPCs are mobilized endogenously in response to tissue ischemia or exogenously by cytokine therapy and thereby augment neovascularization of ischemic tissues.
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                Author and article information

                Journal
                Stem Cells Int
                Stem Cells Int
                SCI
                Stem Cells International
                Hindawi Publishing Corporation
                1687-966X
                1687-9678
                2016
                30 November 2015
                : 2016
                : 7057894
                Affiliations
                1Department of Cardiovascular Surgery of First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou, Jiangsu 215006, China
                2Department of Cardiovascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
                3Department of Cardiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China
                Author notes
                *Zhenya Shen: zhenyashen@ 123456sina.cn and

                Academic Editor: Isotta Chimenti

                Article
                10.1155/2016/7057894
                4677258
                26697079
                15639f17-f971-4dbe-b9eb-26c9eae4b8e4
                Copyright © 2016 Yizhou Ye et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 June 2015
                : 31 August 2015
                : 13 September 2015
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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