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The inhibition of sphingomyelin synthase 1 activity induces collecting duct cells to lose their epithelial phenotype
Authors:Yamila Romina Brandán  Edith del Valle Guaytima  Nicolás Octavio Favale  Lucila Gisele Pescio  Norma B Sterin-Speziale  María Gabriela Márquez
Institution:1. Instituto de Investigaciones en Ciencias de la Salud Humana (IICSHUM), Universidad Nacional de La Rioja, Av. Luis Vernet 1000, 5300 La Rioja, Argentina;2. Instituto de Química y Físico-Química Biológica (IQUIFIB) -CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina;3. Cátedra de Biología Celular, Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina
Abstract:Epithelial tissue requires that cells attach to each other and to the extracellular matrix by the assembly of adherens junctions (AJ) and focal adhesions (FA) respectively. We have previously shown that, in renal papillary collecting duct (CD) cells, both AJ and FA are located in sphingomyelin (SM)-enriched plasma membrane microdomains. In the present work, we investigated the involvement of SM metabolism in the preservation of the epithelial cell phenotype and tissue organization. To this end, primary cultures of renal papillary CD cells were performed. Cultured cells preserved the fully differentiated epithelial phenotype as reflected by the presence of primary cilia. Cells were then incubated for 24 h with increasing concentrations of D609, a SM synthase (SMS) inhibitor. Knock-down experiments silencing SMS 1 and 2 were also performed. By combining biochemical and immunofluorescence studies, we found experimental evidences suggesting that, in CD cells, SMS 1 activity is essential for the preservation of cell-cell adhesion structures and therefore for the maintenance of CD tissue/tubular organization. The inhibition of SMS 1 activity induced CD cells to lose their epithelial phenotype and to undergo an epithelial-mesenchymal transition (EMT) process.
Keywords:Collecting duct cells  Sphingomyelin synthase  Epithelial-mesenchymal transition  Adherens junctions
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