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The sphingosine 1‐phosphate receptor S1P 2 triggers hepatic wound healing
Author(s) -
Serriere-Lanneau Valérie,
Teixeira-Clerc Fatima,
Li Liying,
Schippers Marlies,
Wries Willie,
Julien Boris,
Tran-Van-Nhieu Jeanne,
Manin Sylvie,
Poelstra Klaas,
Chun Jerold,
Carpentier Stéphane,
Levade Thierry,
Mallat Ariane,
Lotersztajn Sophie
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6889com
Subject(s) - sphingosine 1 phosphate , sphingosine kinase , sphingosine , liver injury , wound healing , sphingosine kinase 1 , endocrinology , platelet derived growth factor receptor , medicine , hepatocyte , hepatic stellate cell , microbiology and biotechnology , biology , receptor , immunology , growth factor , biochemistry , in vitro
Sphingosine 1‐phosphate (S1P) is a bio‐active sphingolipid produced by sphingosine kinase (SphK1 and 2). We previously showed that S1P receptors (S1P 1, S1P 2, and S1P 3 ) 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 hepato‐cyte proliferation and matrix remodeling. Acute liver injury was associated with the induction of S1P 2, S1P 3, SphK1, and SphK2 mRNAs and increased SphK activ‐ity, with no change in S1P 1 expression. Necrosis, inflammation, and hepatocyte regeneration were similar in S1P 2 −/− and wild‐type (WT) mice. However, compared with WT mice, S1P 2 −/− mice displayed reduced accumulation of hMF, as shown by lower induction of smooth muscle α‐actin mRNA and lower induction of TIMP‐1, TGF‐β1, and PDGF‐BB mRNAs, overall reflecting reduced activation of remodeling in response to liver injury. The wound healing response was similar in S1P 3 −/− 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 S1P 2 and SphK1 mRNAs, increased SphK activity, and S1P 2 induced PDGF‐BB mRNA. These effects were blunted in S1P 2 −/− cells, and S1P 2 −/− hMF exhibited reduced mitogenic and comitogenic responses to S1P. These results unravel a novel major role of S1P 2 in the wound healing response to acute liver injury by a mechanism involving enhanced proliferation of hMF. –Serriere‐Lanneau, V., Teixeira‐Clerc, F., Li, L., Schippers, M., de Wries, W., Julien, B., Tran‐Van‐Nhieu, J., Manin, S., Poelstra, K., Chun, J., Carpentier, S., Levade, T., Mallat, A., Lotersztajn, S. The sphingosine 1‐phosphate receptor S1P 2 triggers hepatic wound healing. FASEB J. 21, 2005–2013 (2007)