Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPK and SAPK/JNK pathways

  • Authors:
    • Gen Kuroyanagi
    • Takanobu Otsuka
    • Naohiro Yamamoto
    • Rie Matsushima‑Nishiwaki
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations

  • Published online on: March 26, 2015     https://doi.org/10.3892/etm.2015.2389
  • Pages: 2303-2310
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Abstract

Resveratrol, which is found in grape and berry skins and red wine, is generally known to be beneficial for human health due to its anti‑inflammation and antioxidant effects. We have recently reported that transforming growth factor‑β (TGF‑β) stimulates vascular endothelial growth factor (VEGF) synthesis through Smad‑independent pathways, such as the p38 mitogen‑activated protein (MAP) kinase, p44/p42 MAP kinase and stress‑activated protein kinase/c‑Jun N‑terminal kinase (SAPK/JNK) pathways, in osteoblast‑like MC3T3‑E1 cells. The aim of the present study was to investigate the effect of resveratrol on the TGF‑β‑induced VEGF synthesis and the mechanism in osteoblast‑like MC3T3‑E1 cells. Resveratrol significantly suppressed the TGF‑β‑stimulated release of VEGF and the VEGF mRNA expression levels. SRT1720, a synthetic sirtuin 1 (SIRT1) activator, also reduced the VEGF release and the mRNA levels. With regard to the intracellular signaling in the TGF‑β‑stimulated VEGF synthesis, resveratrol and SRT1720 significantly attenuated the phosphorylation of p44/p42 MAP kinase and SAPK/JNK stimulated by TGF‑β; however, the TGF‑β‑induced phosphorylation of Smad2 and p38 MAP kinase was hardly affected by resveratrol or SRT1720. These results strongly suggest that the TGF‑β‑stimulated VEGF synthesis is suppressed by resveratrol through the inhibition of p44/p42 MAP kinase and SAPK/JNK in osteoblasts, and that the suppressive effect is mediated, at least in part, via SIRT1 activation.
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June-2015
Volume 9 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Kuroyanagi G, Otsuka T, Yamamoto N, Matsushima‑Nishiwaki R, Kozawa O and Tokuda H: Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPK and SAPK/JNK pathways. Exp Ther Med 9: 2303-2310, 2015
APA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Matsushima‑Nishiwaki, R., Kozawa, O., & Tokuda, H. (2015). Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPK and SAPK/JNK pathways. Experimental and Therapeutic Medicine, 9, 2303-2310. https://doi.org/10.3892/etm.2015.2389
MLA
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPK and SAPK/JNK pathways". Experimental and Therapeutic Medicine 9.6 (2015): 2303-2310.
Chicago
Kuroyanagi, G., Otsuka, T., Yamamoto, N., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."Resveratrol suppresses TGF-β-induced VEGF synthesis in osteoblasts: Inhibition of the p44/p42 MAPK and SAPK/JNK pathways". Experimental and Therapeutic Medicine 9, no. 6 (2015): 2303-2310. https://doi.org/10.3892/etm.2015.2389