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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

フォーマット:
論文
責任表示:
Watanabe, Toshifumi ; Tajima, Hidehiro ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Ohnishi, Ichiro ; Takamura, Hiroyuki ; Ninomiya, Itasu ; Kitagawa, Hirohisa ; Fushida, Sachio ; Tani, Takashi ; Fujimura, Takashi ; Ohta, Tetsuo ; Wakayama, Tomohiko ; Iseki, Shoichi ; Harada, Shinichi
言語:
英語
出版情報:
Spandidos Publications, 2011-12
著者名:
Watanabe, Toshifumi
Tajima, Hidehiro
Hayashi, Hironori
Nakagawara, Hisatoshi
Ohnishi, Ichiro
Takamura, Hiroyuki
Ninomiya, Itasu
Kitagawa, Hirohisa
Fushida, Sachio
Tani, Takashi
Fujimura, Takashi
Ohta, Tetsuo
Wakayama, Tomohiko
Iseki, Shoichi
Harada, Shinichi
続きを見る
掲載情報:
International Journal of Molecular Medicine
ISSN:
1107-3756  CiNii Articles  Webcat Plus  JAIRO
巻:
28
通号:
6
開始ページ:
919
終了ページ:
925
バージョン:
publisher
概要:
金沢大学医薬保健研究域医学系<br />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 o rgans. 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.<br />Embargo Period 6 months 続きを見る
URL:
http://hdl.handle.net/2297/00049836

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