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Lysophosphatidic acid stimulates cell migration of satellite cells. A role for the sphingosine kinase/sphingosine 1‐phosphate axis
Author(s) -
Cencetti Francesca,
Bruno Gennaro,
Blescia Sabrina,
Bernacchioni Caterina,
Bruni Paola,
Donati Chiara
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12955
Subject(s) - lysophosphatidic acid , sphingosine , sphingosine 1 phosphate , sphingosine kinase , microbiology and biotechnology , motility , lipid signaling , cell migration , biology , rho associated protein kinase , gene silencing , receptor , g protein coupled receptor , kinase , cell , signal transduction , biochemistry , gene
Regulation of the motility of skeletal muscle precursor cells, such as satellite cells, is critically important for their proper recruitment at the site of tissue damage, and ultimately for its correct repair. Here we show that lysophosphatidic acid ( LPA ), which is well‐recognized as a powerful bioactive agent, strongly stimulates cell migration of activated murine satellite cells. The biological effect exerted by LPA was found to be induced via activation of LPA 1 and LPA 3 , being abolished by cell treatment with the antagonist Ki16425, and severely impaired by si RNA ‐mediated down‐regulation of the two receptor isoforms. In contrast, silencing of LPA 2 potentiated the stimulation of cell motility by LPA , suggesting that it is negatively coupled to cell migration. Pharmacological inhibition of both sphingosine kinase ( SK ) isoforms using VPC 96047, or the selective blocking of SK 1 using VPC 96091, abolished cell responsiveness to LPA ; in agreement, gene silencing of SK 1 or SK 2 significantly reduced the biological effect of LPA . Moreover, the LPA ‐dependent stimulation of cell chemotaxis was found to be impaired by down‐regulation of the sphingosine 1‐phosphate (S1P) receptors S1P 1 or S1P 4 by specific si RNA s. In summary, the results obtained support the notion that the sphingosine kinase/sphingosine 1‐phosphate ( SK /S1P) axis is critically involved in the mechanism by which LPA elicits its pro‐migratory action. This study provides compelling new information on the regulatory mechanisms of satellite cell motility, and reinforces the view that the SK /S1P signaling pathway plays a crucial role in the control of skeletal muscle precursor cell biology.