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The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production

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Abstract

In recent years, special attention has been paid to finding new pro-angiogenic factors which could be used in gene therapy of vascular diseases such as critical limb ischaemia (CLI). Angiogenesis, the formation of new blood vessels, is a complex process dependent on different cytokines, matrix proteins, growth factors and other pro- or anti-angiogenic stimuli. Numerous lines of evidence suggest that key mediators of angiogenesis, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) together with fibroblast growth factor2 (FGF2) are involved in regulation of the normal and pathological process of angiogenesis. However, less information is available on the complex interactions between these and other angiogenic factors. The aim of this study was to characterise the effect of fibroblast growth factor2 on biological properties of human endothelial progenitor cells with respect to the expression level of other regulatory cytokines. Ectopic expression of FGF2 in EP cells stimulates their pro-angiogenic behaviour, leading to increased proliferation, migration and tube formation abilities. Moreover, we show that the expression profile of VEGF and other pro-angiogenic cytokines, such as HGF, MCP2, and interleukins, is affected differently by FGF2 in EPC. In conclusion, we provide evidence that FGF2 directly affects not only the biological properties of EP cells but also the expression pattern and secretion of numerous chemocytokines. Our results suggest that FGF2 could be applied in therapeutic approaches for CLI and other ischaemic diseases of the vascular system in vivo.

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Abbreviations

CLI:

Critical limb ischaemia

EPCs:

Endothelial progenitor cells

FGF2:

Basic fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HGF:

Hepatocyte growth factor

HGFR:

Hepatocyte growth factor receptor

MCP2:

Monocyte chemoattractant protein-2

PBS:

Phosphate buffered saline

RT-PCR:

Real-time polymerase chain reaction

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular growth factor receptor

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Funding

This publication is part of the WroVasc Project–Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund within the Innovative Economy Operational Programme 2007-2013 and realised at the Regional Specialist Hospital, Research and Development Centre in Wroclaw. ‘European Funds—for the development of innovative economy.’

Author Contributions

ML. and A.R. designed the research, performed the experiments, analysed the data and wrote the manuscript; D.B. conceived the experiments; M.P. and C.K. provided the endothelial cell model; D.B., T.D. and W.W. revised the manuscript.

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Author notes

  1. Agata Radwańska

    Present address: Institut de Biologie Valrose, CNRS UMR 7277, Faculte des Sciences, Universite Nice-Sophia Antipolis, ParcValrose, 28 Avenue Valrose, 06108, Nice cedex, France

Authors and Affiliations

  1. WroVasc — Integrated Cardiovascular Centre, Regional Specialist Hospital, Research and Development Centre, Kamienskiego 73a, Wrocław, Poland

    Monika Litwin, Agata Radwańska, Maria Paprocka, Tadeusz Dobosz, Wojciech Witkiewicz & Dagmara Baczyńska

  2. Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

    Maria Paprocka

  3. Centre de Biophysique Moléculaire, CNRS, 45071, Orléans Cedex 2, France

    Claudine Kieda

  4. Laboratory of Molecular Technique, Institute of Forensic Medicine, Medical University of Wrocław, Wrocław, Poland

    Tadeusz Dobosz & Dagmara Baczyńska

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  1. Monika Litwin
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Correspondence to Monika Litwin.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Litwin, M., Radwańska, A., Paprocka, M. et al. The role of FGF2 in migration and tubulogenesis of endothelial progenitor cells in relation to pro-angiogenic growth factor production. Mol Cell Biochem 410, 131–142 (2015). https://doi.org/10.1007/s11010-015-2545-5

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  • DOI: https://doi.org/10.1007/s11010-015-2545-5

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