title: Cannabinoid receptors as therapeutic targets for dialysis-induced peritoneal fibrosis.
abstract: BACKGROUND
  Long-term exposure to bioincompatible peritoneal dialysis solutions is frequently complicated with peritoneal fibrosis and ultrafiltration failure. As cannabinoid receptor (CBR) ligands have been reported to be beneficial to ameliorate the process of liver fibrosis, we strove to investigate their therapeutic potential to prevent peritoneal fibrosis.
  
  
  METHODS
  We used the rat model of peritoneal fibrosis induced by intraperitoneal injection of methylglyoxal and in vitro mesothelial cell culture to test the effects of CBR ligands, including the type 1 CBR (CB(1)R) antagonist and the type 2 CBR (CB(2)R) agonist.
  
  
  RESULTS
  In the methylglyoxal model, both intraperitoneal CB(1)R antagonist (AM281) and CB(2)R agonist (AM1241) treatment significantly ameliorated peritoneal fibrosis. In addition, CB(1)R antagonist was able to alleviate TGF-β(1)-induced dedifferentiation of mesothelial cells and to maintain epithelial integrity in vitro.
  
  
  CONCLUSIONS
  Intraperitoneal administration of CBR ligands (CB(1)R antagonist and CB(2)R agonist) offers a potential therapeutic strategy to reduce dialysis-induced peritoneal fibrosis and to prolong the peritoneal survival in peritoneal dialysis patients.
authors.affiliation: Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Yang
authors.forename: Yat-Pang
authors.initials: YP
authors.lastname: Chau
authors.forename: Hsi-Tzu
authors.initials: HT
authors.lastname: Lee
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Kuo
authors.forename: Oscar K
authors.initials: OK
authors.lastname: Lee
authors.forename: An-Hang
authors.initials: AH
authors.lastname: Yang
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D063387:Cannabinoid Receptor Antagonists / Q000627:therapeutic use*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011765:Pyruvaldehyde; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid / Q000378:metabolism*
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D043882:Receptors, Cannabinoid; D011765:Pyruvaldehyde