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

被引：52

作者：

Watanabe, Toshifumi ^{[1
,2
]}

Tajima, Hidehiro ^{[2
]}

Hironori, Hayashi ^{[2
]}

Nakagawara, Hisatoshi ^{[2
]}

Ohnishi, Ichiro ^{[2
]}

Takamura, Hiroyuki ^{[2
]}

Ninomiya, Itasu ^{[2
]}

Kitagawa, Hirohisa ^{[2
]}

Fushida, Sachio ^{[2
]}

Tani, Takashi ^{[2
]}

Fujimura, Takashi ^{[2
]}

Ota, Tetsuo ^{[2
]}

Wakayama, Tomohiko ^{[3
]}

Iseki, Shoichi ^{[3
]}

Harada, Shinichi ^{[4
]}

机构：

[1] Toyama Prefectural Cent Hosp, Dept Surg, Toyama 9308550, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kanazawa, Ishikawa 9208641, Japan

[3] Kanazawa Univ, Grad Sch Med Sci, Dept Histol & Embryol, Kanazawa, Ishikawa 9208641, Japan

[4] Kanazawa Univ, Grad Sch Med Sci, Ctr Biomed Res & Educ, Kanazawa, Ishikawa 9208641, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2011年 / 28卷 / 06期

关键词：

liver fibrosis; hepatic stellate cell; transforming growth factor-beta; valproate; HISTONE DEACETYLASE INHIBITOR; SKIN FIBROBLASTS; GENE-EXPRESSION; TRICHOSTATIN-A; CANCER; ACID; LIVER; GROWTH-FACTOR-BETA-1; DIFFERENTIATION; PROLIFERATION;

D O I：

10.3892/ijmm.2011.768

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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-beta 1 (TGF-beta 1) 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 alpha 1 (COLIAI) and TGF-beta 1 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.

引用

页码：919 / 925

页数：7

共 29 条

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