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Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.

Donati, C; Marseglia, G; Magi, A; Serratì, S; Cencetti, F; Bernacchioni, C; Nannetti, G; ... Bruni, P; + view all (2011) Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6. PLoS One , 6 (5) , Article e20389. 10.1371/journal.pone.0020389. Green open access


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Different cells can contribute to repair following vascular injury by differentiating into smooth muscle (SM) cells; however the extracellular signals involved are presently poorly characterized. Mesoangioblasts are progenitor cells capable of differentiating into various mesoderm cell types including SM cells. In this study the biological action exerted by the pleiotropic sphingolipid sphingosine 1-phosphate (S1P) in human mesoangioblasts has been initially investigated by cDNA microarray analysis. Obtained data confirmed the anti-apoptotic action of this sphingolipid and identified for the first time a strong differentiating action toward SM cells. Quantitative mRNA and protein analysis corroborated the microarray results demonstrating enhanced expression of myogenic marker proteins and regulation of the expression of transcription factor GATA6 and its co-regulator, LMCD1. Importantly, GATA6 up-regulation induced by S1P was responsible for the enhanced expression of SM-specific contractile proteins. Moreover, by specific gene silencing experiments GATA6 was critical in the pro-differentiating activity of the cytokine TGFβ. Finally, the pharmacological inhibition of endogenous S1P formation in response to TGFβ abrogated GATA6 up-regulation, supporting the view that the S1P pathway plays a physiological role in mediating the pro-myogenic effect of TGFβ. This study individuates GATA6 as novel player in the complex transcriptional regulation of mesoangioblast differentiation into SM cells and highlights a role for S1P to favour vascular regeneration.

Type: Article
Title: Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0020389
Publisher version: http://dx.doi.org/10.1371/journal.pone.0020389
Language: English
Additional information: © 2011 Donati et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3101247 This work was supported by funds from University of Florence (ex-60%) to P. Bruni and C. Donati, www.unifi.it, Ente Cassa di Risparmio di Firenze to F. Torricelli, www.crf.it, Fondazione Cassa di Risparmio di Lucca to P.Bruni, www.fondazionecarilucca.it. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.
Keywords: Blotting, Western, Carrier Proteins, Cell Differentiation, Cells, Cultured, Co-Repressor Proteins, GATA6 Transcription Factor, Humans, LIM Domain Proteins, Lysophospholipids, Microscopy, Fluorescence, Myocytes, Smooth Muscle, Oligonucleotide Array Sequence Analysis, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Sphingosine, Stem Cells
URI: http://discovery.ucl.ac.uk/id/eprint/1342448
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