PPAR-gamma ligands up-regulate basic fibroblast growth factor-induced VEGF release through amplifying SAPK/JNK activation in osteoblasts.

Eisuke Yasuda; Haruhiko Tokuda; Akira Ishisaki; Kouseki Hirade; Yosuke Kanno; Yoshiteru Hanai; Norimi Nakamura; Takahiro Noda; Yoshihiro Katagiri; Osamu Kozawa

doi:10.1016/j.bbrc.2004.12.163

PubMed · 15670761

PPAR-gamma ligands up-regulate basic fibroblast growth factor-induced VEGF release through amplifying SAPK/JNK activation in osteoblasts.

Eisuke Yasuda·Haruhiko Tokuda·Akira Ishisaki·Kouseki Hirade·Yosuke Kanno·Yoshiteru Hanai·Norimi Nakamura·Takahiro Noda·Yoshihiro Katagiri·Osamu Kozawa

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Abstract

We previously reported that basic fibroblast growth factor (FGF-2) activates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates the VEGF release. In the present study, we investigated the effects of ciglitazone and pioglitazone, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands, on the VEGF release by FGF-2 in MC3T3-E1 cells. The FGF-2-induced VEGF release was significantly enhanced by ciglitazone. The amplifying effect of ciglitazone was dose-dependent between 0.1 and 10 microM. Pioglitazone had a similar effect on the VEGF release. GW9662, an antagonist of PPAR-gamma, reduced the effects of ciglitazone and pioglitazone. Ciglitazone or pioglitazone markedly enhanced the phosphorylation of SAPK/JNK induced by FGF-2 without affecting both the FGF-2-induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. GW9662 markedly reduced the amplification by ciglitazone of the SAPK/JNK phosphorylation. Taken together, these results strongly suggest that PPAR-gamma ligands up-regulate FGF-2-stimulated VEGF release resulting from amplifying activation of SAPK/JNK in osteoblasts.

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3T3 Cells Animals Dose-Response Relationship, Drug Enzyme Activation Fibroblast Growth Factor 2 JNK Mitogen-Activated Protein Kinases Ligands Mice PPAR gamma Pioglitazone Thiazolidinediones Up-Regulation Vascular Endothelial Growth Factor A p38 Mitogen-Activated Protein Kinases Journal Article Research Support, Non-U.S. Gov't

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Eisuke Yasuda, Haruhiko Tokuda, Akira Ishisaki, Kouseki Hirade, Yosuke Kanno, Yoshiteru Hanai, Norimi Nakamura, Takahiro Noda, Yoshihiro Katagiri, Osamu Kozawa. 2005-03-04. PPAR-gamma ligands up-regulate basic fibroblast growth factor-induced VEGF release through amplifying SAPK/JNK activation in osteoblasts.. https://doi.org/10.1016/j.bbrc.2004.12.163

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