Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2

被引：106

作者：

Ikeda, Hitoshi ^{[1
,2
]}

Watanabe, Naoko ^{[1
,2
]}

Ishii, Isao ^{[3
]}

Shimosawa, Tatsuo ^{[1
]}

Kume, Yukio ^{[1
]}

Tomiya, Tomoaki ^{[2
]}

Inoue, Yukiko ^{[2
]}

Nishikawa, Takako ^{[2
]}

Ohtomo, Natsuko ^{[2
]}

Tanoue, Yasushi ^{[2
]}

Iitsuka, Satoko ^{[1
]}

Fujita, Ryoto ^{[1
]}

Omata, Masao ^{[2
]}

Chun, Jerold ^{[4
]}

Yatomi, Yutaka ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Clin Lab Med, Bunkyo Ku, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Gastroenterol, Bunkyo Ku, Tokyo, Japan

[3] Gunma Univ, Grad Sch Med, Dept Mol & Cellular Neurobiol, Gunma, Japan

[4] Scripps Res Inst, Dept Mol Biol, Helen L Dorris Child & Adolescent Neuropsychiat, La Jolla, CA 92037 USA

来源：

JOURNAL OF LIPID RESEARCH | 2009年 / 50卷 / 03期

基金：

美国国家卫生研究院;

关键词：

liver regeneration; liver fibrosis; hepatocyte; hepatic stellate cell; hepatic myofibroblast; HEPATIC STELLATE CELLS; IN-VIVO; LYSOPHOSPHOLIPID RECEPTORS; LYMPHOCYTE EGRESS; ACTIVATION; MYOFIBROBLASTS; S1P(2); SPHINGOSINE-1-PHOSPHATE; PROLIFERATION; INVOLVEMENT;

D O I：

10.1194/jlr.M800496-JLR200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, stimulates proliferation and contractility in hepatic stellate cells, the principal matrix-producing cells in the liver, and inhibits proliferation via S1P receptor 2 (S1P(2)) in hepatocytes in rats in vitro. A potential role of S1P and S1P(2) in liver regeneration and fibrosis was examined in S1P(2)-deficient mice. Nuclear 5-bromo-2'-deoxy-uridine labeling, proliferating cell nuclear antigen (PCNA) staining in hepatocytes, and the ratio of liver weight to body weight were enhanced at 48 h in S1P(2)-deficient mice after a single carbon tetrachloride (CCl4) injection. After dimethylnitrosamine (DMN) administration with a lethal dose, PCNA staining in hepatocytes was enhanced at 48 h and survival rate was higher in S1P(2)-deficient mice. Serum aminotransferase level was unaltered in those mice compared with wild-type mice in both CCl4- and DMN-induced liver injury, suggesting that S1P(2) inactivation accelerated regeneration not as a response to enhanced liver damage. After chronic CCl4 administration, fibrosis was less apparent, with reduced expression of smooth-muscle a-actin-positive cells in the livers of S1P(2)-deficient mice, suggesting that S1P(2) inactivation ameliorated CCl4-induced fibrosis due to the decreased accumulation of hepatic stellate cells. Thus, S1P plays a significant role in regeneration and fibrosis after liver injury via S1P(2).-Ikeda, H., N. Watanabe, I. Ishii, T. Shimosawa, Y. Kume, T. Tomiya, Y. Inoue, T. Nishikawa, N. Ohtomo, Y. Tanoue, S. Iitsuka, R. Fujita, M. Omata, J. Chun, and Y. Yatomi. Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2. J. Lipid Res. 2009. 50: 556-564.

引用

页码：556 / 564

页数：9

共 43 条

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The Forkhead transcription factor Fox01 regulates proliferation and transdifferentiation of hepatic stellate cells [J].