Anna Laurenzana, Francesca Cencetti, Simona Serrati, Gennaro Bruno, Lukasz Japtok, Francesca Bianchini, Eugenio Torre, Gabriella Fibbi, Mario Del Rosso, Paola Bruni, Chiara Donati
- The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating peiicyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1phosphate (SIP) is a bioactive sphingolipid that derives from sphingomyelin catabolism and regulates biological functions in cell survival, proliferation, and differentiation. In this study, we aimed to identify the role of SIP axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (HMVEC)) in the formation of capillary-like structures. We demonstrated that the SIP biosynthetic pathway brought about by sphingosine kinases (SK) SKI and SK2 as well as spinster homolog 2 (SPNS2) transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers and for the formation and stabilization of capillary-like structures in a 3D Matrigel culture.The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating peiicyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1phosphate (SIP) is a bioactive sphingolipid that derives from sphingomyelin catabolism and regulates biological functions in cell survival, proliferation, and differentiation. In this study, we aimed to identify the role of SIP axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (HMVEC)) in the formation of capillary-like structures. We demonstrated that the SIP biosynthetic pathway brought about by sphingosine kinases (SK) SKI and SK2 as well as spinster homolog 2 (SPNS2) transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers and for the formation and stabilization of capillary-like structures in a 3D Matrigel culture. Moreover, the conditioned medium (CM) harvested from HMVEC, where SKI, 5K2, and SPNS2 were down-regulated, exerted a significantly diminished effect on MAB capillary morphogenesis and migration. Notably, we demonstrated that S I Pi and Si p3 receptors were positively involved in CM-induced capillary-like formation and migration, while S I P2 exerted a negative role on CM-induced migratory action of MAB. Finally, SK inhibition as well as MAB SlPi and S1P3 down-regulation impaired HMVEC-MAB cross-talk significantly reducing in vivo angiogenesis evaluated by Matrigel plug assay. These findings individuate novel targets for the employment of MAB in vascular-related pathologic conditions.…
MetadatenVerfasserangaben: | Anna Laurenzana, Francesca Cencetti, Simona Serrati, Gennaro Bruno, Lukasz JaptokGND, Francesca Bianchini, Eugenio Torre, Gabriella Fibbi, Mario Del Rosso, Paola Bruni, Chiara Donati |
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DOI: | https://doi.org/10.1007/s00109-015-1292-0 |
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ISSN: | 0946-2716 |
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ISSN: | 1432-1440 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/25952146 |
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Titel des übergeordneten Werks (Englisch): | Journal of molecular medicine |
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Verlag: | Springer |
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Verlagsort: | New York |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Erstveröffentlichung: | 2015 |
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Erscheinungsjahr: | 2015 |
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Datum der Freischaltung: | 27.03.2017 |
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Freies Schlagwort / Tag: | Endothelial cells; Mesoangioblasts; Migration; Morphogenesis; Sphingosine kinase |
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Band: | 93 |
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Ausgabe: | 10 |
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Seitenanzahl: | 13 |
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Erste Seite: | 1145 |
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Letzte Seite: | 1157 |
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Fördernde Institution: | Fondi di Ateneo; Ente Cassa di Risparmio di Firenze; Associazione
Italiana Ricerca sul Cancro (AIRC) [14266] |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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Peer Review: | Referiert |
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