Characterization of epithelial-to-mesenchymal transition of mesothelial cells in a mouse model of chronic peritoneal exposure to high glucose dialysate.
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.
Aroeira
Luiz S
LS
Unidad de Investigación and Servicio de Nefrología, Hospital Universitario La Paz.
Loureiro
Jesús
J
González-Mateo
Guadalupe T
GT
Fernandez-Millara
Vanessa
V
del Peso
Gloria
G
Sánchez-Tomero
José Antonio
JA
Ruiz-Ortega
Marta
M
Bajo
M Auxiliadora
MA
López-Cabrera
Manuel
M
Selgas
Rafael
R
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D008648:Mesoderm / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D015314:Dialysis Solutions; D005947:Glucose