Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation by human mesoangioblasts

Verfasser / Beitragende:
[Anna Laurenzana, Francesca Cencetti, Simona Serratì, Gennaro Bruno, Lukasz Japtok, Francesca Bianchini, Eugenio Torre, Gabriella Fibbi, Mario Del Rosso, Paola Bruni, Chiara Donati]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Medicine, 93/10(2015-10-01), 1145-1157
Format:
Artikel (online)
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024 7 0 |a 10.1007/s00109-015-1292-0  |2 doi 
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245 0 0 |a Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation by human mesoangioblasts  |h [Elektronische Daten]  |c [Anna Laurenzana, Francesca Cencetti, Simona Serratì, Gennaro Bruno, Lukasz Japtok, Francesca Bianchini, Eugenio Torre, Gabriella Fibbi, Mario Del Rosso, Paola Bruni, Chiara Donati] 
520 3 |a The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating pericyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1-phosphate (S1P) 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 S1P axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (H-MVEC)) in the formation of capillary-like structures. We demonstrated that the S1P biosynthetic pathway brought about by sphingosine kinases (SK) SK1 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 H-MVEC, where SK1, SK2, and SPNS2 were down-regulated, exerted a significantly diminished effect on MAB capillary morphogenesis and migration. Notably, we demonstrated that S1P1 and S1P3 receptors were positively involved in CM-induced capillary-like formation and migration, while S1P2 exerted a negative roleon CM-induced migratory action of MAB. Finally, SK inhibition as well as MAB S1P1 and S1P3 down-regulation impaired H-MVEC-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. Key message: • Down-regulation of SK1/2 in H-MVEC impaired vessel formation when cultured with MAB. • H-MVEC SPNS2 is critical for morphogenesis and migration induced by H-MVEC CM of MAB. • CM from SK1- and SK2-siRNA H-MVEC impaired morphogenesis and migration of MAB. • S1P1/3 were involved on CM-induced morphogenesis and migration of MAB. • Matrigel plug assay showed the role of S1P axis in MAB-endothelial cell interaction. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a Mesoangioblasts  |2 nationallicence 
690 7 |a Endothelial cells  |2 nationallicence 
690 7 |a Sphingosine kinase  |2 nationallicence 
690 7 |a Migration  |2 nationallicence 
690 7 |a Morphogenesis  |2 nationallicence 
690 7 |a SK : Sphingosine kinase  |2 nationallicence 
690 7 |a S1P : Sphingosine 1-phosphate  |2 nationallicence 
690 7 |a FCS : Fetal calf serum  |2 nationallicence 
690 7 |a siRNA : Short-interfering RNA  |2 nationallicence 
690 7 |a SCR : Scrambled  |2 nationallicence 
690 7 |a CM : Conditioned medium  |2 nationallicence 
690 7 |a PBS : Phosphate-buffered saline  |2 nationallicence 
690 7 |a DMEM : Dulbecco's modified Eagle's medium  |2 nationallicence 
690 7 |a BSA : Bovine serum albumin  |2 nationallicence 
690 7 |a TGFβ : Transforming growth factor beta  |2 nationallicence 
690 7 |a SPNS2 : Spinster homolog 2  |2 nationallicence 
690 7 |a bFGF : Basic fibroblast growth factor  |2 nationallicence 
690 7 |a VEGF : Vascular endothelial growth factor  |2 nationallicence 
690 7 |a MAPK : Mitogen-activated protein kinase  |2 nationallicence 
690 7 |a PI3K : Phosphatidylinositol 3-kinase  |2 nationallicence 
690 7 |a SCID : Severe combined immunodeficiency  |2 nationallicence 
700 1 |a Laurenzana  |D Anna  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Cencetti  |D Francesca  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Serratì  |D Simona  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Bruno  |D Gennaro  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Japtok  |D Lukasz  |u Faculty of Mathematics and Natural Science, Institute of Nutritional Science, Department of Toxicology, University of Potsdam, Arthur-Scheunert Allee 114-116, 14558, Potsdam, Nuthetal, Germany  |4 aut 
700 1 |a Bianchini  |D Francesca  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Torre  |D Eugenio  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Fibbi  |D Gabriella  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Del Rosso  |D Mario  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Bruni  |D Paola  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
700 1 |a Donati  |D Chiara  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
773 0 |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/10(2015-10-01), 1145-1157  |x 0946-2716  |q 93:10<1145  |1 2015  |2 93  |o 109 
856 4 0 |u https://doi.org/10.1007/s00109-015-1292-0  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00109-015-1292-0  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Laurenzana  |D Anna  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Cencetti  |D Francesca  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Serratì  |D Simona  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bruno  |D Gennaro  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Japtok  |D Lukasz  |u Faculty of Mathematics and Natural Science, Institute of Nutritional Science, Department of Toxicology, University of Potsdam, Arthur-Scheunert Allee 114-116, 14558, Potsdam, Nuthetal, Germany  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bianchini  |D Francesca  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Torre  |D Eugenio  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fibbi  |D Gabriella  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Del Rosso  |D Mario  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Bruni  |D Paola  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Donati  |D Chiara  |u Dipartimento di Scienze Biomediche Sperimentali e Cliniche "Mario Serio”, Università di Firenze, Viale G.B. Morgagni 50, 50134, Florence, Italy  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/10(2015-10-01), 1145-1157  |x 0946-2716  |q 93:10<1145  |1 2015  |2 93  |o 109