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Sphingosine 1‐phosphate regulates myogenic differentiation: a major role for S1P 2 receptor
Author(s) -
Donati Chiara,
Meacci Elisabetta,
Nuti Francesca,
Becciolini Laura,
Farnararo Marta,
Bruni Paola
Publication year - 2005
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.04-1780fje
Subject(s) - c2c12 , sphingosine 1 phosphate , myogenesis , microbiology and biotechnology , myogenin , sphingolipid , myocyte , biology , mapk/erk pathway , sphingosine , myosin , signal transduction , sphingosine 1 phosphate receptor , cell growth , cellular differentiation , sphingosine kinase , receptor , biochemistry , gene
In this study a novel biological activity of sphingosine 1‐phosphate (S1P) in C2C12 myoblasts was identified. In these cells the bioactive lipid profoundly regulated myogenesis exerting an antimitogenic activity, by reducing serum‐induced cell proliferation, and acting as powerful prodifferentiating agent by enhancing the expression of myogenic differentiation markers such as myogenin, myosin heavy chain, and caveolin‐3. The S1P‐dependent diminution of serum‐induced labeled thymidine incorporation was abrogated by antisense oligodeoxyribonucleotides (ODN) to S1P 2 , but not to S1P 1 or S1P 3 receptor, also expressed in C2C12 cells, implicating S1P 2 in the biological response. Using antisense ODN and short interfering RNA treatment, we highlighted the key role played by S1P 2 in the S1P‐dependent induction of muscle‐specific gene products. Notably, S1P 2 overexpression increased the content of myogenic markers and hastened the onset of differentiated muscle phenotype in comparison with control cells. Cell treatment with pertussis toxin did not affect the biological responses to S1P, ruling out the involvement of Gi‐mediated events in the signaling promoted by the sphingolipid. Among the various signaling pathways activated by S1P, the activation of ERK1/ERK2 and p38 MAPK, both identified as downstream effectors of S1P 2 , was required for the inhibition of cell proliferation and the stimulation of myogenic differentiation, respectively.