title: Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.
abstract: BACKGROUND
  Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs.
  
  
  METHODS
  Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed.
  
  
  RESULTS
  HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT.
  
  
  CONCLUSIONS
  Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression.
authors.affiliation: Pharmacology Dept., Centre for Research and Advanced Studies National Polytechnic Institute, Mexico.
authors.forename: Carmen
authors.initials: C
authors.lastname: Retana
authors.affiliation: Physiology, Biophysics and Neurosciences Dept., Centre for Research and Advanced Studies National Polytechnic Institute, Mexico.
authors.forename: Elsa
authors.initials: E
authors.lastname: Sanchez
authors.affiliation: Dept. of Nephrology, Hospital Central Norte de PEMEX, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Perez-Lopez
authors.affiliation: Unidad Medica Alta Especialidad, Hospital General la Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Unidad Medica Alta Especialidad, Hospital General la Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Lagunas
authors.affiliation: Dept. of Nephrology, Hospital Regional No. 1 del IMSS, Mexico.
authors.forename: Carmen
authors.initials: C
authors.lastname: Cruz
authors.affiliation: Dept. of Nephrology, Hospital Juarez de Mexico, Mexico.
authors.forename: Socorro
authors.initials: S
authors.lastname: Vital
authors.affiliation: Physiology, Biophysics and Neurosciences Dept., Centre for Research and Advanced Studies National Polytechnic Institute, Mexico.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Reyes
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D001706:Biopsy; D015153:Blotting, Western; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010539:Permeability; D019108:Tight Junctions / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D015314:Dialysis Solutions; D014212:Tretinoin
keywords: Continuous ambulatory peritoneal dialysis; claudins; high transporter; human peritoneal mesothelial cells; low transporter; occludin; peritoneal permeability; retinoic acid