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

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 includi...

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Autores principales: Chiara Donati, Giuseppina Marseglia, Alberto Magi, Simona Serratì, Francesca Cencetti, Caterina Bernacchioni, Genni Nannetti, Matteo Benelli, Silvia Brunelli, Francesca Torricelli, Giulio Cossu, Paola Bruni
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:850ca9b65edd4ef696d16b132e2be5d52021-11-18T06:53:23ZSphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.1932-620310.1371/journal.pone.0020389https://doaj.org/article/850ca9b65edd4ef696d16b132e2be5d52011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21629665/?tool=EBIhttps://doaj.org/toc/1932-6203Different 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.Chiara DonatiGiuseppina MarsegliaAlberto MagiSimona SerratìFrancesca CencettiCaterina BernacchioniGenni NannettiMatteo BenelliSilvia BrunelliFrancesca TorricelliGiulio CossuPaola BruniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e20389 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Chiara Donati
Giuseppina Marseglia
Alberto Magi
Simona Serratì
Francesca Cencetti
Caterina Bernacchioni
Genni Nannetti
Matteo Benelli
Silvia Brunelli
Francesca Torricelli
Giulio Cossu
Paola Bruni
Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
description 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.
format article
author Chiara Donati
Giuseppina Marseglia
Alberto Magi
Simona Serratì
Francesca Cencetti
Caterina Bernacchioni
Genni Nannetti
Matteo Benelli
Silvia Brunelli
Francesca Torricelli
Giulio Cossu
Paola Bruni
author_facet Chiara Donati
Giuseppina Marseglia
Alberto Magi
Simona Serratì
Francesca Cencetti
Caterina Bernacchioni
Genni Nannetti
Matteo Benelli
Silvia Brunelli
Francesca Torricelli
Giulio Cossu
Paola Bruni
author_sort Chiara Donati
title Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
title_short Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
title_full Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
title_fullStr Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
title_full_unstemmed Sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. A role for GATA6.
title_sort sphingosine 1-phosphate induces differentiation of mesoangioblasts towards smooth muscle. a role for gata6.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/850ca9b65edd4ef696d16b132e2be5d5
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