Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line

  • Authors:
    • Toshifumi Watanabe
    • Hidehiro Tajima
    • Hayashi Hironori
    • Hisatoshi Nakagawara
    • Ichiro Ohnishi
    • Hiroyuki Takamura
    • Itasu Ninomiya
    • Hirohisa Kitagawa
    • Sachio Fushida
    • Takashi Tani
    • Takashi Fujimura
    • Tetsuo Ota
    • Tomohiko Wakayama
    • Shoichi Iseki
    • Shinichi Harada
  • View Affiliations

  • Published online on: August 5, 2011     https://doi.org/10.3892/ijmm.2011.768
  • Pages: 919-925
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Abstract

Histone acetylation and deacetylation have been thought to be related to gene expression, and there are many reports indicating that histone deacetylase inhibitors (HDACis) exert antifibrogenic effects in several organs. In injured livers, hepatic stellate cells (HSCs) are activated in response to profibrogenic mediators and produce large amounts of extracellular matrix. In particular, transforming growth factor-β1 (TGF-β1) is considered as a key factor in accelerating hepatic fibrosis because it is released from activated HSCs and further stimulates them. The present study aimed to clarify whether sodium valproate (VPA) has suppressive effects on cultured human HSCs (LI90). We showed that treatment with VPA had no significantly suppressive effect on cell proliferation at a concentration of 1 mM, which corresponded approximately to the serum concentration obtained by the administration of a clinical dose. However, VPA prevented the morphological changes characteristic for activation and inhibited the expression of collagen type 1 α1 (COL1A1) and TGF-β1 in activated LI90 cells at the mRNA and protein levels. Our results support the hypothesis that VPA exerts antifibrogenic activity with little cytotoxicity at 1 mM, and HDACis are expected to be used in clinical practice for the treatment of fibrotic diseases.

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December 2011
Volume 28 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Watanabe T, Tajima H, Hironori H, Nakagawara H, Ohnishi I, Takamura H, Ninomiya I, Kitagawa H, Fushida S, Tani T, Tani T, et al: Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line. Int J Mol Med 28: 919-925, 2011.
APA
Watanabe, T., Tajima, H., Hironori, H., Nakagawara, H., Ohnishi, I., Takamura, H. ... Harada, S. (2011). Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line. International Journal of Molecular Medicine, 28, 919-925. https://doi.org/10.3892/ijmm.2011.768
MLA
Watanabe, T., Tajima, H., Hironori, H., Nakagawara, H., Ohnishi, I., Takamura, H., Ninomiya, I., Kitagawa, H., Fushida, S., Tani, T., Fujimura, T., Ota, T., Wakayama, T., Iseki, S., Harada, S."Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line". International Journal of Molecular Medicine 28.6 (2011): 919-925.
Chicago
Watanabe, T., Tajima, H., Hironori, H., Nakagawara, H., Ohnishi, I., Takamura, H., Ninomiya, I., Kitagawa, H., Fushida, S., Tani, T., Fujimura, T., Ota, T., Wakayama, T., Iseki, S., Harada, S."Sodium valproate blocks the transforming growth factor (TGF)-β1 autocrine loop and attenuates the TGF-β1-induced collagen synthesis in a human hepatic stellate cell line". International Journal of Molecular Medicine 28, no. 6 (2011): 919-925. https://doi.org/10.3892/ijmm.2011.768