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Article Open Access

Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts

  • Authors:
    • Jun Mizutani
    • Haruhiko Tokuda
    • Rie Matsushima-Nishiwaki
    • Kenji Kato
    • Akira Kondo
    • Hideo Natsume
    • Osamu Kozawa
    • Takanobu Otsuka
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-Cho, Mizuho-Ku, Nagoya 467-8601, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan
    Copyright: © Mizutani et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 550-556
    |
    Published online on: January 23, 2012
       https://doi.org/10.3892/ijmm.2012.893
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Abstract

It is generally recognized that AMP-activated protein kinase (AMPK) acts as a key regulator of energy homeostasis. We have previously shown that transforming growth factor-β (TGF-β) stimulates synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether AMPK is involved in the TGF-β-stimulated VEGF synthesis in osteoblast-like MC3T3-E1 cells. TGF-β time-dependently induced the phosphorylation of the AMPK α-subunit (Thr172) and the AMPK β-subunit (Ser108). Compound C, an AMPK inhibitor, significantly reduced the TGF-β-stimulated VEGF release. The inhibitory effect of compound C was also observed in normal human osteoblasts (NHOst). Although compound C failed to affect the TGF-β-induced phosphorylation of SAPK/JNK, p38 MAP kinase or Smad2, it markedly suppressed the TGF-β-induced phosphorylation of both MEK1/2 and p44/p42 MAP kinase. In addition, compound C significantly suppressed the VEGF mRNA expression induced by TGF-β. Taken together, our results strongly suggest that AMPK is involved in TGF-β-stimulated VEGF synthesis, and that it functions at a point upstream of MEK1/2.
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Copy and paste a formatted citation
Spandidos Publications style
Mizutani J, Tokuda H, Matsushima-Nishiwaki R, Kato K, Kondo A, Natsume H, Kozawa O and Otsuka T: Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts. Int J Mol Med 29: 550-556, 2012.
APA
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H. ... Otsuka, T. (2012). Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts. International Journal of Molecular Medicine, 29, 550-556. https://doi.org/10.3892/ijmm.2012.893
MLA
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H., Kozawa, O., Otsuka, T."Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts". International Journal of Molecular Medicine 29.4 (2012): 550-556.
Chicago
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H., Kozawa, O., Otsuka, T."Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts". International Journal of Molecular Medicine 29, no. 4 (2012): 550-556. https://doi.org/10.3892/ijmm.2012.893
Copy and paste a formatted citation
x
Spandidos Publications style
Mizutani J, Tokuda H, Matsushima-Nishiwaki R, Kato K, Kondo A, Natsume H, Kozawa O and Otsuka T: Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts. Int J Mol Med 29: 550-556, 2012.
APA
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H. ... Otsuka, T. (2012). Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts. International Journal of Molecular Medicine, 29, 550-556. https://doi.org/10.3892/ijmm.2012.893
MLA
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H., Kozawa, O., Otsuka, T."Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts". International Journal of Molecular Medicine 29.4 (2012): 550-556.
Chicago
Mizutani, J., Tokuda, H., Matsushima-Nishiwaki, R., Kato, K., Kondo, A., Natsume, H., Kozawa, O., Otsuka, T."Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts". International Journal of Molecular Medicine 29, no. 4 (2012): 550-556. https://doi.org/10.3892/ijmm.2012.893
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