Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

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

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • 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, Jerold
  • Yatomi, Y.

publication date

  • 2009

journal

  • Journal of Lipid Research  Journal

abstract

  • 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).

subject areas

  • Animals
  • Carbon Tetrachloride
  • Dimethylnitrosamine
  • Female
  • Hepatocytes
  • Liver
  • Liver Cirrhosis
  • Liver Regeneration
  • Lysophospholipids
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proliferating Cell Nuclear Antigen
  • Receptors, Lysosphingolipid
  • Sphingosine
scroll to property group menus

Research

keywords

  • hepatic myofibroblast
  • hepatic stellate cell
  • hepatocyte
  • liver fibrosis
  • liver regeneration
scroll to property group menus

Identity

PubMed Central ID

  • PMC2638109

International Standard Serial Number (ISSN)

  • 0022-2275

Digital Object Identifier (DOI)

  • 10.1194/jlr.M800496-JLR200

PubMed ID

  • 18955732
scroll to property group menus

Additional Document Info

start page

  • 556

end page

  • 564

volume

  • 50

issue

  • 3

©2019 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support