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

Mol Cell Biochem. 2015 Dec;410(1-2):131-42. doi: 10.1007/s11010-015-2545-5. Epub 2015 Aug 28.

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.

Keywords: Angiogenesis; Basic fibroblast growth factor; Cytokines; Endothelial progenitor cells; Vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenic Proteins / metabolism*
  • Cell Line
  • Cell Movement*
  • Cell Proliferation
  • Chemokine CCL8 / metabolism
  • Endothelial Progenitor Cells / metabolism*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Interleukins / metabolism
  • Neovascularization, Physiologic*
  • Signal Transduction
  • Time Factors
  • Transfection
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenic Proteins
  • CCL8 protein, human
  • Chemokine CCL8
  • HGF protein, human
  • Interleukins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Hepatocyte Growth Factor