Sphingomyelin Synthesis Modulates E-Cadherin Maturation and Renal Epithelial Cell Differentiation

FREIRE PT; ROMERO DJ; SANTACREU BJ; FAVALE NO

Córdoba

Congreso; LII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2016

SAIB

We have demonstrated that sphingomyelin (SM) biosynthesis is essential for hypertonicity-induced MDCK cell differentiation. Under inhibition of SM synthesis, MDCK cells instead to differentiate switch to mesenchymal phenotype thus performing an epithelial to mesenchymal transition (EMT). To study the sphingolipid metabolic pathway involved in such process, confluent MDCK cells were subjected to hypertonicity and concomitantly sphingomyelin synthase (SMS) was inhibited by pharmacological and knockdown strategies. Both strategies showed alteration of polarized phenotype with acquisition of mesenchymal phenotype. EMT can be initiated by the alteration of E-cadherin/beta-catenin/alpha-catenin complex. We observed that the inhibition of SM synthesis did not modify the total E-cadherin level. However, we observed an alteration in E-cadherin maturation. Particularly, D609 an SMS inhibitor and SMS1-siRNA induced an accumulation of the precursor of E-cadherin (with higher molecular weight) with a decrease of mature E- cadherin level. These results suggest that SM synthesis is involved in E-cadherin maturation and adherent junctions? formation.