Involvement of β1-integrin up-regulation in basic fibroblast growth factor- and epidermal growth factor-induced proliferation of mouse neuroepithelial cells

Yusuke Suzuki, Makoto Yanagisawa, Hirokazu Yagi, Yoshihiko Nakatani, Robert K Yu

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In neural stem cells, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) promote cell proliferation and self-renewal. In the bFGF- and EGF-responsive neural stem cells, β1-integrin also plays important roles in crucial cellular processes, including proliferation, migration, and apoptosis. The cross-talk of the signaling pathways mediated by these growth factors and β1-integrin, however, has not been fully elucidated. Here we report a novel molecular mechanism through which bFGF or EGF promotes the proliferation of mouse neuroepithelial cells (NECs). In the NECs, total β1-integrin expression levels and proliferation were dose-dependently increased by bFGF but not by EGF. EGF rather than bFGF strongly induced the increase of β1-integrin localization on the NEC surface. bFGF- and EGF-induced β1-integrin up-regulation and proliferation were inhibited after treatment with a mitogen-activated protein kinase kinase inhibitor, U0126, which indicates the dependence on the mitogen-activated protein kinase pathway. Involvement of β1-integrin in bFGF- and EGF-induced proliferation was confirmed by the finding that NEC proliferation and adhesion to fibronectin-coated dishes were inhibited by knockdown of β1-integrin using small interfering RNA. On the other hand, apoptosis was induced in NECs treated with RGD peptide, a small β1-integrin inhibitor peptide with the Arg-Gly-Asp motif, but it was independent of β1-integrin expression levels. Those results suggest that regulation of β1-integrin expression/ localization is involved in cellular processes, such as proliferation, induced by bFGF and EGF in NECs. The mechanism underlying the proliferation through β1-integrin would not be expected to be completely identical, however, for bFGF and EGF.

Original languageEnglish (US)
Pages (from-to)18443-18451
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number24
DOIs
StatePublished - Jun 11 2010

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Neuroepithelial Cells
Fibroblast Growth Factor 2
Epidermal Growth Factor
Integrins
Up-Regulation
Neural Stem Cells
Cell proliferation
Stem cells
Cell Proliferation
Apoptosis
Cell adhesion
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Fibronectins
Cell Adhesion
Small Interfering RNA
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Involvement of β1-integrin up-regulation in basic fibroblast growth factor- and epidermal growth factor-induced proliferation of mouse neuroepithelial cells. / Suzuki, Yusuke; Yanagisawa, Makoto; Yagi, Hirokazu; Nakatani, Yoshihiko; Yu, Robert K.

In: Journal of Biological Chemistry, Vol. 285, No. 24, 11.06.2010, p. 18443-18451.

Research output: Contribution to journalArticle

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