PPAR‑γ agonist rosiglitazone protects rat peritoneal mesothelial cells against peritoneal dialysis solution‑induced damage

Mol Med Rep. 2017 Apr;15(4):1786-1792. doi: 10.3892/mmr.2017.6196. Epub 2017 Feb 13.

Abstract

Long-term peritoneal dialysis (PD) leads to ultrafiltration failure (UFF). Peritoneal mesothelial cells, which form the innermost monolayer of the peritoneal cavity, have been shown to regulate various responses, including inflammation, in UFF. The present study was designed to investigate the effect of the peroxisome proliferator‑activated receptor‑γ (PPAR‑γ) agonist, rosiglitazone, on peritoneal dialysis solution (PDS)‑induced injuries in rat peritoneal mesothelial cells (RPMCs). RPMCs were cultured for different durations and with different concentrations of PDS. The gene expression levels of aquaporin‑1 (AQP‑1) and zonula occluden‑1 (ZO‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The protein levels of AQP‑1, ZO‑1 and PPAR‑γ were measured using western blot analysis. Interleukin (IL)‑6 and IL‑8 were detected using ELISA. The RPMCs were damaged by stimulation with 4.25% PDS for 72 h. The expression levels of AQP‑1 and ZO‑1 were increased, and the secretion of IL‑6 and IL‑8 were decreased by rosiglitazone. The use of the PPAR‑γ inhibitor, GW‑9662, completely prevented the effects of rosiglitazone. These results indicated that PDS exposure stimulated an inflammatory response in the RPMCs. The PPAR‑γ activator, rosiglitazone, appeared to relieve the injury by inhibiting inflammation, and regulating the expression of AQP‑1 and ZO‑1, however further investigations are required to elucidate the potential underlying mechanism.

MeSH terms

  • Animals
  • Aquaporin 1 / analysis
  • Aquaporin 1 / genetics
  • Dialysis Solutions / adverse effects*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / pathology
  • Interleukin-6 / analysis
  • Interleukin-6 / metabolism
  • Interleukin-8 / analysis
  • Interleukin-8 / metabolism
  • Male
  • PPAR gamma / agonists*
  • PPAR gamma / analysis
  • PPAR gamma / metabolism
  • Peritoneal Dialysis / adverse effects*
  • Peritoneum / cytology
  • Peritoneum / drug effects*
  • Peritoneum / pathology
  • Protective Agents / therapeutic use*
  • RNA, Messenger / genetics
  • Rats, Sprague-Dawley
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*
  • Zonula Occludens-1 Protein / analysis
  • Zonula Occludens-1 Protein / genetics

Substances

  • Aqp1 protein, rat
  • Dialysis Solutions
  • Interleukin-6
  • Interleukin-8
  • PPAR gamma
  • Protective Agents
  • RNA, Messenger
  • Thiazolidinediones
  • Tjp1 protein, rat
  • Zonula Occludens-1 Protein
  • Rosiglitazone
  • Aquaporin 1