title: Pioglitazone reduces peritoneal fibrosis via inhibition of TGF-β, MMP-2, and MMP-9 in a model of encapsulating peritoneal sclerosis.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-β) were increased in peritoneal dialysis patients with encapsulating peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are the major regulators of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The objective of this study was to investigate the effect of pioglitazone (Pio), a synthetic PPAR-γ ligand, on the development of peritoneal fibrosis in CG-induced EPS rats.
  
  
  METHODS
  Thirty-two Wistar albino rats were intraperitoneally injected with saline (C group n = 8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was administered orally to another group of CG injected rats (the CG + Pio group, n = 8) and to another control group (Pio group, n = 8) from initiation to the end of this study. After 14 days of Pio administration, the rats were killed and the parietal and visceral peritoneum were harvested. TGF-β, MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a morphological examination of the peritoneal tissues were performed.
  
  
  RESULTS
  Pio significantly inhibited thickening of the submesothelial layer, fibrosis, and inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP-9, TIMP-1, and TGF-β activities.
  
  
  CONCLUSIONS
  Pio, via MMP and TGF-β inhibition, may lessen accumulation of peritoneal extracellular matrix and fibrosis to some extent in an EPS model and might be a new approach to the amelioration of EPS.
authors.affiliation: Department of Nephrology, School of Medicine, Dokuz Eylul University, Izmir, Balcova, Turkey. fundasaglam@yahoo.com
authors.forename: Funda
authors.initials: F
authors.lastname: Saglam
authors.forename: Zahide
authors.initials: Z
authors.lastname: Cavdar
authors.forename: Sulen
authors.initials: S
authors.lastname: Sarioglu
authors.forename: Efsun
authors.initials: E
authors.lastname: Kolatan
authors.forename: Gulgun
authors.initials: G
authors.lastname: Oktay
authors.forename: Osman
authors.initials: O
authors.lastname: Yilmaz
authors.forename: Taner
authors.initials: T
authors.lastname: Camsari
mesh_terms: D000818:Animals; D005260:Female; D061965:Matrix Metalloproteinase Inhibitors; D056627:Peritoneal Fibrosis / Q000517:prevention & control*; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077205:Pioglitazone