1. Academic Validation
  2. Sphingosine-1-phosphate receptor 2 plays a dual role depending on the stage of cell differentiation in renal epithelial cells

Sphingosine-1-phosphate receptor 2 plays a dual role depending on the stage of cell differentiation in renal epithelial cells

  • Life Sci. 2023 Jan 18;316:121404. doi: 10.1016/j.lfs.2023.121404.
Daniela Judith Romero 1 Lucila Gisele Pescio 1 Bruno Jaime Santacreu 1 Jazmín María Mosca 2 Norma Beatriz Sterin-Speziale 3 Nicolás Octavio Favale 4
Affiliations

Affiliations

  • 1 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas "Profesor Dr. Alejandro C. Paladini" (IQUIFIB), Buenos Aires, Argentina.
  • 2 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina.
  • 3 CONICET - Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas "Profesor Dr. Alejandro C. Paladini" (IQUIFIB), Laboratorio Nacional de Investigación y Servicios de Péptidos y Proteínas - Espectrometría de Masa (LANAIS PROEM), Buenos Aires, Argentina.
  • 4 Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Biología Celular y Molecular, Buenos Aires, Argentina; CONICET - Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas "Profesor Dr. Alejandro C. Paladini" (IQUIFIB), Buenos Aires, Argentina. Electronic address: nofaval@ffyb.uba.ar.
Abstract

Epithelial renal cells have the ability to adopt different cellular phenotypes through epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET). These processes are increasingly recognized as important repair factors following acute renal tubular injury. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid with impact on proliferation, growth, migration, and differentiation which has significant implication in various diseases including Cancer and kidney fibrosis. Here we demonstrated that S1P can exert by activating S1P receptor 2 (S1PR2) different functions depending on the stage of cell differentiation. We observed that the differences in the migratory profile of Madin-Darby canine kidney (MDCK) cells depend both on their stage of cell differentiation and the activity of S1PR2, a receptor that can either promote or inhibit the migratory process. Meanwhile in non-differentiated cells S1PR2 activation avoids migration, it is essential on fully differentiated cells. This is the first time that an antagonist effect of S1PR2 was reported for the same cell type. Moreover, in fully differentiated cells, S1PR2 activation is crucial for the progression of EMT - characterized by adherent junctions disassembly, β-catenin and SNAI2 nuclear translocation and vimentin expression- and depends on ERK 1/2 activation and nuclear translocation. These findings provide a new perspective about the different S1PR2 functions depending on the stage of cell differentiation that can be critical to the modulation of renal epithelial cell plasticity, potentially paving the way for innovative research with pathophysiologic relevance.

Keywords

Epithelial-mesenchymal plasticity; Epithelial-mesenchymal transition; Sphingosine-1-phosphate; Sphingosine-1-phosphate receptor 2.

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