title: Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis: role of vascular endothelial growth factor.
abstract: BACKGROUND
  During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids that cause epithelial-to-mesenchymal transition of mesothelial cells, fibrosis, and angiogenesis. Ultrafiltration failure is associated with high transport rates and increased vascular surface, indicating the implication of vascular endothelial growth factor (VEGF). Sources of VEGF in vivo in PD patients remain unclear. We analyzed the correlation between epithelial-to-mesenchymal transition of mesothelial cells and both VEGF level and peritoneal functional decline.
  
  
  METHODS
  Effluent mesothelial cells were isolated from 37 PD patients and analyzed for mesenchymal conversion. Mass transfer coefficient for creatinine (Cr-MTC) was used to evaluate peritoneal function. VEGF concentration was measured by using standard procedures. Peritoneal biopsy specimens from 12 PD patients and 6 controls were analyzed immunohistochemically for VEGF and cytokeratin expression.
  
  
  RESULTS
  Nonepithelioid mesothelial cells from effluent produced a greater amount of VEGF ex vivo than epithelial-like mesothelial cells (P < 0.001). Patients whose drainage contained nonepithelioid mesothelial cells had greater serum VEGF levels than those with epithelial-like mesothelial cells in their effluent (P < 0.01). VEGF production ex vivo by effluent mesothelial cells correlated with serum VEGF level (r = 0.6; P < 0.01). In addition, Cr-MTC correlated with VEGF levels in culture (r = 0.8; P < 0.001) and serum (r = 0.35; P < 0.05). Cr-MTC also was associated with mesothelial cell phenotype. VEGF expression in stromal cells, retaining mesothelial markers, was observed in peritoneal biopsy specimens from high-transporter patients.
  
  
  CONCLUSIONS
  These results suggest that mesothelial cells that have undergone epithelial-to-mesenchymal transition are the main source of VEGF in PD patients and therefore may be responsible for a high peritoneal transport rate.
authors.affiliation: Servicio de Nefrología, Hospital Universitario de la Princesa, Madrid, Spain.
authors.forename: Luiz S
authors.initials: LS
authors.lastname: Aroeira
authors.forename: Abelardo
authors.initials: A
authors.lastname: Aguilera
authors.forename: Rafael
authors.initials: R
authors.lastname: Selgas
authors.forename: Marta
authors.initials: M
authors.lastname: Ramírez-Huesca
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Pérez-Lozano
authors.forename: Antonio
authors.initials: A
authors.lastname: Cirugeda
authors.forename: M Auxiliadora
authors.initials: MA
authors.lastname: Bajo
authors.forename: Gloria
authors.initials: G
authors.lastname: del Peso
authors.forename: José A
authors.initials: JA
authors.lastname: Sánchez-Tomero
authors.forename: José A
authors.initials: JA
authors.lastname: Jiménez-Heffernan
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Cabrera
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002454:Cell Differentiation / Q000187:drug effects; D002463:Cell Membrane Permeability; D002478:Cells, Cultured / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005947:Glucose / Q000008:administration & dosage; D015312:Hemodialysis Solutions / Q000493:pharmacokinetics / Q000494:pharmacology*; D006465:Hemoperitoneum / Q000209:etiology / Q000473:pathology; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010530:Peritoneal Dialysis; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010538:Peritonitis / Q000209:etiology / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*
chemical_list: D015312:Hemodialysis Solutions; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007633:Keratins; D005947:Glucose