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Int. J. Mol. Sci. 2018, 19(1), 139; https://doi.org/10.3390/ijms19010139

Lysophosphatidic Acid Signaling Axis Mediates Ceramide 1-Phosphate-Induced Proliferation of C2C12 Myoblasts

1
Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale GB Morgagni 50, 50134 Firenze, Italy
2
Istituto Interuniversitario di Miologia (IIM), Italy
3
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain
4
Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
*
Author to whom correspondence should be addressed.
Received: 24 November 2017 / Revised: 23 December 2017 / Accepted: 28 December 2017 / Published: 4 January 2018
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Sphingolipids are not only crucial for membrane architecture but act as critical regulators of cell functions. The bioactive sphingolipid ceramide 1-phosphate (C1P), generated by the action of ceramide kinase, has been reported to stimulate cell proliferation, cell migration and to regulate inflammatory responses via activation of different signaling pathways. We have previously shown that skeletal muscle is a tissue target for C1P since the phosphosphingolipid plays a positive role in myoblast proliferation implying a role in muscle regeneration. Skeletal muscle displays strong capacity of regeneration thanks to the presence of quiescent adult stem cells called satellite cells that upon trauma enter into the cell cycle and start proliferating. However, at present, the exact molecular mechanism by which C1P triggers its mitogenic effect in myoblasts is lacking. Here, we report for the first time that C1P stimulates C2C12 myoblast proliferation via lysophosphatidic acid (LPA) signaling axis. Indeed, C1P subsequently to phospholipase A2 activation leads to LPA1 and LPA3 engagement, which in turn drive Akt (protein kinase B) and ERK1/2 (extracellular signal-regulated kinases 1/2) activation, thus stimulating DNA synthesis. The present findings shed new light on the key role of bioactive sphingolipids in skeletal muscle and provide further support to the notion that these pleiotropic molecules might be useful therapeutic targets for skeletal muscle regeneration. View Full-Text
Keywords: lysophosphatidic acid (LPA); ceramide 1-phosphate (C1P); lysophosphatidic acid receptor (LPAR); skeletal muscle; myoblast proliferation lysophosphatidic acid (LPA); ceramide 1-phosphate (C1P); lysophosphatidic acid receptor (LPAR); skeletal muscle; myoblast proliferation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Bernacchioni, C.; Cencetti, F.; Ouro, A.; Bruno, M.; Gomez-Muñoz, A.; Donati, C.; Bruni, P. Lysophosphatidic Acid Signaling Axis Mediates Ceramide 1-Phosphate-Induced Proliferation of C2C12 Myoblasts. Int. J. Mol. Sci. 2018, 19, 139.

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