IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SPHINGOSINE-1-PHOSPHATE MAINTAINS TISSUE HOMEOSTASIS IN DIFFERENTIATED EPITHELIAL CELLS
Autor/es:
SANTACREU BJ; FAVALE NO; STERIN SPEZIALE NB
Lugar:
Iguazú
Reunión:
Congreso; 56th International Conference on the Bioscience of Lipids (ICBL); 2015
Institución organizadora:
ICBL
Resumen:
Sphingosine 1-Phophate (S1P) is a sphingolipid mediator involved in cellular fate that acts both extracellularly as ligand for cell surface receptors (S1PR) and intracellularly as second messenger. We have demonstrated that hypertonicity induces epithelial cell differentiation which depends on changes in sphingolipid metabolism. Epithelial cell differentiation requires a specific intracellular organization as well as the correct monolayer formation. This process requires an adequate removing of apoptotic cells followed by a rapid closes of empty spaces, thus preserving tissue permeability and integrity. This physiological process is known as cell extrusion and was linked with S1P cellular effects. So, we studied the involvement of sphingosine kinase (SK) activity in MDCK cell differentiation and monolayer architecture preservation. For this, confluent MDCK cells were subjected to hypertonic medium in the presence or absence of SK inhibitors (SKi II or L-threo-dihydrosphingosine). After 48 h, cell phenotype and monolayer architecture were visualized by fluorescence microscopy, evaluating actin cytoskeleton organization and adherens junction formation. By performing a confocal z-plane reconstruction we visualized extruding cells and found that the inhibition of SK evoked an alteration of efficient cell extrusion. This effect was reverted by exogenous S1P. Concomitantly, the inhibition of SK induced an increase in the expression of S1PR2 with a clear plasma membrane distribution. These results suggest that extracellular S1P, by the interaction with S1PR2 could be involved in tissue homeostasis modulating of the correct cell extrusion.