| 18955732 |
Ikeda H, Watanabe N, Ishii I, Shimosawa T, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Iitsuka S, Fujita R, Omata M, Chun J, Yatomi Y: Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2. J Lipid Res. 2009 Mar;50(3):556-64. Epub 2008 Oct 27.
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 (CCl (4)) 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 CCl (4)- and DMN-induced liver injury, suggesting that S1P (2) inactivation accelerated regeneration not as a response to enhanced liver damage. After chronic CCl (4) administration, fibrosis was less apparent, with reduced expression of smooth-muscle alpha-actin-positive cells in the livers of S1P (2)-deficient mice, suggesting that S1P (2) inactivation ameliorated CCl (4)-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). |
11(0,0,1,6) |