Sphingosine 1-Phosphate Mediates Proliferation and Survival of Mesoangioblasts

¹ Dipartimento di Scienze Biochimiche, Università di Firenze, 50134 Firenze, Istituto Interuniversitario di Miologia (IIM)
² Dipartimento di Scienze Biochimiche, Università di Firenze, 50134 Firenze
³ Stem Cell Research Institute, Istituto Scientifico H San Raffaele, 20132 Milano, Italy; Dipartimento di Medicina Sperimentale, Università di Milano- Bicocca, 20052 Monza, Italy
⁴ IRCCS E. Medea, 23842, Bosisio Parini, Italy; Dipartimento di Scienze Precliniche LITA-Vialba, Università di Milano, 20157 Milano, Italy
⁵ Stem Cell Research Institute, Istituto Scientifico H San Raffaele, 20132 Milano, Italy; Dipartimento di Biologia, Università di Milano, 20130 Milano

^* To whom correspondence should be addressed. E-mail: paola.bruni{at}unifi.it.

	Abstract

Mesoangioblasts are stem cells capable of differentiating in various mesodermal tissues and are presently regarded as suitable candidates for cell therapy of muscle degenerative diseases as well as myocardial infarction. The enhancement of their proliferation and survival after injection in vivo could greatly improve their ability of repopulating damaged tissues. In this study we show that the bioactive sphingolipid sphingosine 1-phosphate (S1P) regulates critical functions of mesoangioblast cell biology. S1P evoked a full mitogenic response in mesoangioblasts, measured by labeled thymidine incorporation and cell counting. Moreover, S1P strongly counteracted the apoptotic process triggered by stimuli as diverse as serum deprivation, C₂-ceramide or staurosporine, assessed by cell counting as well as histone-associated fragments and caspase-3 activity determinations. S1P acts both as an intracellular messenger or through specific membrane receptors. Real-time PCR analysis revealed that mesoangioblasts express the S1P-specific receptor S1P₃ and to a minor extent S1P₁ and S1P₂. By employing S1P receptor subtype-specific agonists and antagonists we found that the proliferative response to S1P was mediated mainly by S1P₂ . By contrast, the antiapoptotic effect did not implicate S1P receptors. These findings demonstrate an important role of S1P in mesoangioblast proliferation and survival and indicate that targeting modulation of S1P-dependent signaling pathways may be used to improve the efficiency of muscle repair by these cells.

This article has been cited by other articles:

				C. Zhao, M. J. Fernandes, M. Turgeon, S. Tancrede, J. Di Battista, P. E. Poubelle, and S. G. Bourgoin Specific and overlapping sphingosine-1-phosphate receptor functions in human synoviocytes: impact of TNF-{alpha} J. Lipid Res., November 1, 2008; 49(11): 2323 - 2337. [Abstract] [Full Text] [PDF]