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Vascular endothelial growth factor-C promotes human mesenchymal stem cell migration via an ERK-and FAK-dependent mechanism

  • Masakazu Ishii
  • Manami Takahashi
  • Juri Murakami
  • Takahiro Yanagisawa
  • Masahiro Nishimura
Article
  • 99 Downloads

Abstract

Vascular endothelial cell growth factor-C (VEGF-C) is a member of the VEGF family and plays a role in various biological activities. VEGF-C enhances proliferation and migration of lymphatic endothelial cells and vascular endothelial cells through VEGF receptor 2 (VEGFR2) and/or receptor 3 (VEGFR3), and thereby induces lymphangiogenesis or angiogenesis. However, it remains unclear whether VEGF-C promotes the migration of mesenchymal stem cells (MSCs). Here, we investigated the effects of VEGF-C on the migration of MSCs and evaluated the underlying molecular mechanisms. VEGF-C treatment significantly induced the migration of MSCs, which is accompanied by the promotion of actin cytoskeletal reorganization and focal adhesion assembly. VEGF-C treatment enhanced the phosphorylation of VEGFR2 and VEGFR3 proteins in MSCs, and pretreatment with VEGFR2 and VEGFR3 kinase inhibitors effectively suppressed the VEGF-C-induced MSC migration. In addition, VEGF-C treatment promoted phosphorylation of ERK and FAK proteins in MSCs, and inhibition of VEGFR2 and VEGFR3 signaling pathways abolished the VEGF-C-induced activation of ERK and FAK proteins. Furthermore, treatment with ERK and FAK inhibitors suppressed VEGF-C-induced actin cytoskeletal reorganization and focal adhesion assembly, and then significantly inhibited MSCs migration. These results suggest that VEGF-C-induced MSC migration is mediated via VEGFR2 and VEGFR3, and follows the activation of the ERK and FAK signaling pathway. Thus, VEGF-C may be valuable in tissue regeneration and repair in MSC-based therapy.

Keywords

VEGF-C Mesenchymal stem cells Migration ERK FAK 

Notes

Acknowledgements

This work was in part supported by Grant-in Aid for Scientific Research B (Grant No. 17H04394), and Grant-in Aid for Scientific Research C (Grant No. 15K11169).

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Masakazu Ishii
    • 1
  • Manami Takahashi
    • 1
  • Juri Murakami
    • 1
    • 2
  • Takahiro Yanagisawa
    • 1
  • Masahiro Nishimura
    • 1
  1. 1.Department of Oral and Maxillofacial ProsthodonticsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  2. 2.Department of Oral and Maxillofacial SurgeryKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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