Open Access

VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes

  • Authors:
    • Yasuyuki Igarashi
    • Naoyuki Chosa
    • Shunsuke Sawada
    • Hisatomo Kondo
    • Takashi Yaegashi
    • Akira Ishisaki
  • View Affiliations

  • Published online on: February 25, 2016     https://doi.org/10.3892/ijmm.2016.2502
  • Pages: 1005-1013
  • Copyright: © Igarashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The direction of mesenchymal stem cell (MSC) differentiation is regulated by stimulation with various growth factors and cytokines. We recently established MSC lines, [transforming growth factor-β (TGF-β)-responsive SG‑2 cells, bone morphogenetic protein (BMP)-responsive SG‑3 cells, and TGF-β/BMP-non-responsive SG‑5 cells], derived from the bone marrow of green fluorescent protein-transgenic mice. In this study, to compare gene expression profiles in these MSC lines, we used DNA microarray analysis to characterize the specific gene expression profiles observed in the TGF-β-responsive SG‑2 cells. Among the genes that were highly expressed in the SG‑2 cells, we focused on vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), the gene product of FMS-like tyrosine kinase 4 (Flt4). We found that VEGF-C, a specific ligand of VEGFR3, significantly induced the cell proliferative activity, migratory ability (as shown by Transwell migration assay), as well as the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in the SG‑2 cells. Additionally, VEGF-C significantly increased the expression of prospero homeobox 1 (Prox1) and lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1), which are lymphatic endothelial cell markers, and decreased the expression of osteogenic differentiation marker genes in these cells. By contrast, TGF-β significantly increased the expression of early-phase osteogenic differentiation marker genes in the SG‑2 cells and markedly decreased the expression of lymphatic endothelial cell markers. The findings of our study strongly suggest the following: i) that VEGF-C promotes the proliferative activity and migratory ability of MSCs; and ii) VEGF-C and TGF-β reciprocally regulate MSC commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes, respectively. Our findings provide new insight into the molecular mechanisms underlying the regenerative ability of MSCs.
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April-2016
Volume 37 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Igarashi Y, Chosa N, Sawada S, Kondo H, Yaegashi T and Ishisaki A: VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes. Int J Mol Med 37: 1005-1013, 2016
APA
Igarashi, Y., Chosa, N., Sawada, S., Kondo, H., Yaegashi, T., & Ishisaki, A. (2016). VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes. International Journal of Molecular Medicine, 37, 1005-1013. https://doi.org/10.3892/ijmm.2016.2502
MLA
Igarashi, Y., Chosa, N., Sawada, S., Kondo, H., Yaegashi, T., Ishisaki, A."VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes". International Journal of Molecular Medicine 37.4 (2016): 1005-1013.
Chicago
Igarashi, Y., Chosa, N., Sawada, S., Kondo, H., Yaegashi, T., Ishisaki, A."VEGF-C and TGF-β reciprocally regulate mesenchymal stem cell commitment to differentiation into lymphatic endothelial or osteoblastic phenotypes". International Journal of Molecular Medicine 37, no. 4 (2016): 1005-1013. https://doi.org/10.3892/ijmm.2016.2502