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Perit Dial Int 28(Supplement_5): 29-33
2008
© 2008 International Society for Peritoneal Dialysis
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Articles

CHARACTERIZATION OF EPITHELIAL-TO-MESENCHYMAL TRANSITION OF MESOTHELIAL CELLS IN A MOUSE MODEL OF CHRONIC PERITONEAL EXPOSURE TO HIGH GLUCOSE DIALYSATE

Luiz S. Aroeira1, Jesús Loureiro2, Guadalupe T. González-Mateo1, Vanessa Fernandez-Millara1, Gloria del Peso1, José Antonio Sánchez-Tomero3, Marta Ruiz-Ortega4, M. Auxiliadora Bajo1, Manuel López-Cabrera2,5 and Rafael Selgas1,a

Unidad de Investigación and Servicio de Nefrología1 Hospital Universitario La Paz; Unidad de Biología Molecular2 and Servicio de Nefrología3 Hospital Universitario de la Princesa; Laboratory of Renal and Vascular Research4 Fundación Jiménez Díaz; Centro de Biología Molecular Severo Ochoa5 CSIC-UAM, Cantoblanco, Madrid, Spain

Footnotes

a All the authors belong to the Instituto Reina Sofía de Investigaciones Nefrológicas.

Correspondence to: R. Selgas, Servicio de Nefrología, Hospital Universitario La Paz, Castellana, 261, 28046, Madrid, Spain. rselgas.hulp{at}salud.madrid.org

Animal models of peritoneal dialysis fluid (PDF) exposure are key tools in the study of mechanisms involved in alterations of the peritoneal membrane and in the design of therapies. We recently developed a mouse model of chronic peritoneal exposure to high glucose dialysate. Herein, we make a sequential analysis of the effects of glucose-based PDF on mouse peritoneal membrane and on mesothelium. We demonstrate that chronic exposure to PDF induces thickness and fibrosis of the peritoneal membrane in a time-dependent manner. We also show that mesothelial cells progressively detach and lose cytokeratin expression. In addition, we demonstrate that some mesothelial cells invade the submesothelial space, where they appear as cytokeratin- and alpha-smooth muscle actin-positive cells. These findings demonstrate that epithelial-to-mesenchymal transition (EMT) of mesothelial cells takes place in mouse peritoneum exposed to PDF, validating this model for the study of effects of drugs on the EMT process as a therapy for peritoneal deterioration.

KEY WORDS: Mesothelial cell; epithelial-to-mesenchymal transition; mice model of peritoneal dialysis.






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