TY  - JOUR
A1  - Laurenzana, Anna
A1  - Cencetti, Francesca
A1  - Serrati, Simona
A1  - Bruno, Gennaro
A1  - Japtok, Lukasz
A1  - Bianchini, Francesca
A1  - Torre, Eugenio
A1  - Fibbi, Gabriella
A1  - Del Rosso, Mario
A1  - Bruni, Paola
A1  - Donati, Chiara
T1  - Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation by human mesoangioblasts
JF  - Journal of molecular medicine
N2  - 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.
KW  - Mesoangioblasts
KW  - Endothelial cells
KW  - Sphingosine kinase
KW  - Migration
KW  - Morphogenesis
Y1  - 2015
U6  - https://doi.org/10.1007/s00109-015-1292-0
SN  - 0946-2716
SN  - 1432-1440
VL  - 93
IS  - 10
SP  - 1145
EP  - 1157
PB  - Springer
CY  - New York
ER  -