Prostaglandins differently regulate FGF-2 and FGF receptor expression and induce nuclear translocation in osteoblasts via MAPK kinase
MG Sabbieti, L Marchetti, MG Gabrielli, M Menghi… - Cell and tissue …, 2005 - Springer
MG Sabbieti, L Marchetti, MG Gabrielli, M Menghi, S Materazzi, G Menghi, LG Raisz…
Cell and tissue research, 2005•SpringerWe have previously reported that prostaglandin F 2α (PGF 2α) and its selective agonist
fluprostenol increase basic fibroblast growth factor (FGF-2) mRNA and protein production in
osteoblastic Py1a cells. The present report extends our previous studies by showing that
Py1a cells express FGF receptor-2 (FGFR2) and that treatment with PGF 2α or fluprostenol
decreases FGFR2 mRNA. We have used confocal and electron microscopy to show that,
under PGF 2α stimulation, FGF-2 and FGFR2 proteins accumulate near the nuclear …
fluprostenol increase basic fibroblast growth factor (FGF-2) mRNA and protein production in
osteoblastic Py1a cells. The present report extends our previous studies by showing that
Py1a cells express FGF receptor-2 (FGFR2) and that treatment with PGF 2α or fluprostenol
decreases FGFR2 mRNA. We have used confocal and electron microscopy to show that,
under PGF 2α stimulation, FGF-2 and FGFR2 proteins accumulate near the nuclear …
Abstract
We have previously reported that prostaglandin F2α (PGF2α) and its selective agonist fluprostenol increase basic fibroblast growth factor (FGF-2) mRNA and protein production in osteoblastic Py1a cells. The present report extends our previous studies by showing that Py1a cells express FGF receptor-2 (FGFR2) and that treatment with PGF2α or fluprostenol decreases FGFR2 mRNA. We have used confocal and electron microscopy to show that, under PGF2α stimulation, FGF-2 and FGFR2 proteins accumulate near the nuclear envelope and colocalize in the nucleus of Py1a cells. Pre-treatment with cycloheximide blocks nuclear labelling for FGF-2 in response to PGF2α. Treatment with SU5402 does not block prostaglandin-mediated nuclear internalization of FGF-2 or FGFR2. Various effectors have been used to investigate the signal transduction pathway. In particular, pre-treatment with phorbol 12-myristate 13-acetate (PMA) prevents the nuclear accumulation of FGF-2 and FGFR2 in response to PGF2α. Similar results are obtained by pre-treatment with the protein kinase C (PKC) inhibitor H-7. In addition, cells treated with PGF2α exhibit increased nuclear labelling for the mitogen-activated protein kinase (MAPK), p44/ERK2. Pre-treatment with PMA blocks prostaglandin-induced ERK2 nuclear labelling, as confirmed by Western blot analysis. We conclude that PGF2α stimulates nuclear translocation of FGF-2 and FGFR2 by a PKC-dependent pathway; we also suggest an involvement of MAPK/ERK2 in this process.
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