Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

The sphingosine 1-phosphate receptor S1P2 triggers hepatic wound healing

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

Overview

authors

  • Serriere-Lanneau, V.
  • Teixeira-Clerc, F.
  • Li, L. Y.
  • Schippers, M.
  • de Wries, W.
  • Julien, B.
  • Tran-Van-Nhieu, J.
  • Manin, S.
  • Poelstra, K.
  • Chun, Jerold
  • Carpentier, S.
  • Levade, T.
  • Mallat, A.
  • Lotersztajn, S.

publication date

  • July 2007

journal

  • FASEB Journal  Journal

abstract

  • Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P1, S1P2, and S1P3) are expressed in hepatic myofibroblasts (hMF), a population of cells that triggers matrix remodeling during liver injury. Here we investigated the function of these receptors in the wound healing response to acute liver injury elicited by carbon tetrachloride, a process that associates hepatocyte proliferation and matrix remodeling. Acute liver injury was associated with the induction of S1P2, S1P3, SphK1, and SphK2 mRNAs and increased SphK activity, with no change in S1P1 expression. Necrosis, inflammation, and hepatocyte regeneration were similar in S1P2-/- and wild-type (WT) mice. However, compared with WT mice, S1P2-/- mice displayed reduced accumulation of hMF, as shown by lower induction of smooth muscle alpha-actin mRNA and lower induction of TIMP-1, TGF-beta1, and PDGF-BB mRNAs, overall reflecting reduced activation of remodeling in response to liver injury. The wound healing response was similar in S1P3-/- and WT mice. In vitro, S1P enhanced proliferation of cultured WT hMF, and PDGF-BB further enhanced the mitogenic effect of S1P. In keeping with these findings, PDGF-BB up-regulated S1P2 and SphK1 mRNAs, increased SphK activity, and S1P2 induced PDGF-BB mRNA. These effects were blunted in S1P2-/- cells, and S1P2-/- hMF exhibited reduced mitogenic and comitogenic responses to S1P. These results unravel a novel major role of S1P2 in the wound healing response to acute liver injury by a mechanism involving enhanced proliferation of hMF.

subject areas

  • Acute Disease
  • Animals
  • Carbon Tetrachloride Poisoning
  • Cell Division
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury
  • DNA Replication
  • Enzyme Induction
  • Extracellular Matrix
  • Fibroblasts
  • Gene Expression Regulation
  • Liver Regeneration
  • Lysophospholipids
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myoblasts, Smooth Muscle
  • Necrosis
  • Phosphotransferases (Alcohol Group Acceptor)
  • Platelet-Derived Growth Factor
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-sis
  • Receptors, Lysosphingolipid
  • Sphingosine
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
scroll to property group menus

Research

keywords

  • hepatic myofibroblasts
  • liver
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0892-6638

Digital Object Identifier (DOI)

  • 10.1096/fj.06-6889com

PubMed ID

  • 17341687
scroll to property group menus

Additional Document Info

start page

  • 2005

end page

  • 2013

volume

  • 21

issue

  • 9

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support