Involvement of beta1-integrin up-regulation in basic fibroblast growth factor- and epidermal growth factor-induced proliferation of mouse neuroepithelial cells.
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, beta1-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 beta1-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 beta1-integrin expression levels and proliferation were dose-dependently increased by bFGF but not by EGF. EGF rather than bFGF strongly induced the increase of beta1-integrin localization on the NEC surface. bFGF- and EGF-induced beta1-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 beta1-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 beta1-integrin using small interfering RNA. On the other hand, apoptosis was induced in NECs treated with RGD peptide, a small beta1-integrin inhibitor peptide with the Arg-Gly-Asp motif, but it was independent of beta1-integrin expression levels. Those results suggest that regulation of beta1-integrin expression/localization is involved in cellular processes, such as proliferation, induced by bFGF and EGF in NECs. The mechanism underlying the proliferation through beta1-integrin would not be expected to be completely identical, however, for bFGF and EGF.
Suzuki
Yusuke
Y
Institute of Molecular Medicine and Genetics and Institute of Neuroscience, Medical College of Georgia, Augusta, Georgia 30912, USA.
Yanagisawa
Makoto
M
Yagi
Hirokazu
H
Nakatani
Yoshihiko
Y
Yu
Robert K
RK
D020816:Amino Acid Motifs; D000818:Animals; D019921:Biotinylation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D034622:RNA Interference
D019012:Integrin beta1; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor