@article{oai:kanazawa-u.repo.nii.ac.jp:00043494, author = {田島, 秀浩 and 林, 泰寛 and 中川原, 寿俊 and 高村, 博之 and 二宮, 致 and 北川, 裕久 and 伏田, 幸夫 and 谷, 卓 and 藤村, 隆 and 太田, 哲生 and 若山, 友彦 and 井関, 尚一 and 原田, 真市 and Watanabe, Toshifumi and Tajima, Hidehiro and Hayashi, Hironori and Nakagawara, Hisatoshi and Ohnishi, Ichiro and Takamura, Hiroyuki and Ninomiya, Itasu and Kitagawa, Hirohisa and Fushida, Sachio and Tani, Takashi and Fujimura, Takashi and Ohta, Tetsuo and Wakayama, Tomohiko and Iseki, Shoichi and Harada, Shinichi}, issue = {6}, journal = {International Journal of Molecular Medicine}, month = {Dec}, note = {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., Embargo Period 6 months, 金沢大学医薬保健研究域医学系}, pages = {919--925}, title = {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}, volume = {28}, year = {2011} }