Role of sphingosine-1-phosphate receptor 2 in epitelial cell diferentiation

GRU RB; ROMERO DJ; SANTACREU BJ; CHAVEZ FLORES JC; FAVALE NO

CABA

Congreso; II Reunión Conjunta de Sociedades de BioCiencias; 2017

SAIB-SAIC-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP

Previous results from our laboratory shown that in Madin-Darby canine kidney cells (MDCK), the exposure to a hypertonic medium (300 mM NaCl) induces a differentiated phenotype and this process is related to the sphingolipid metabolism. Sphingosine-1-phosphate (S1P) has been classically associated with the induction of a prolif- erative phenotype and anti-apoptotic activity. However, the partici- pation of S1P in the cell differentiation is not well understood. S1P can act both intracellularly as second messenger and extracellularly as ligand for cell surface receptors (S1PRs). It has been reported that S1P levels decreases during transition to the differentiated state so that prevails mechanisms via S1PRs. For these reasons, we evaluated whether changes in the expression and/or localization of S1PRs are involved in the differentiation process. The expression level of S1PR2 in different stages of differentiation of MDCK cells was assessed by western blotting and did not show signi cant dif- ferences. Instead, immuno uorescence studies showed that during cell differentiation, S1PR2 was progressively enriched at the plasma membrane. In addition, we found that S1PR2 overexpression with plasma membrane localization, altered parameters related to differ- entiation like proliferation rate, maturation of adherent junctions and migration when compared to non-transfected cells. We concluded that a speci c relocation of receptors is a determinant mechanism for acquisition of the differentiated phenotype in MDCK cells. These results suggest a new function for the S1P/ S1PR2 pathway.