title: The role of the TGF/Smad signaling pathway in peritoneal fibrosis induced by peritoneal dialysis solutions.
abstract: BACKGROUND
  Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-beta1/Smad signaling pathway in a chronic PD rat model.
  
  
  METHODS
  Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls.
  
  
  RESULTS
  The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-beta1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-beta1/Smad expression and less expansion of the submesothelial cell layer.
  
  
  CONCLUSIONS
  Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-beta1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism.
authors.affiliation: Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yao
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pawlaczyk
authors.forename: Ernesto Rodríguez
authors.initials: ER
authors.lastname: Ayala
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Styszynski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Breborowicz
authors.forename: Olof
authors.initials: O
authors.lastname: Heimburger
authors.forename: Jia Qi
authors.initials: JQ
authors.lastname: Qian
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Jonas
authors.initials: J
authors.lastname: Axelsson
mesh_terms: D000818:Animals; D015314:Dialysis Solutions / Q000009:adverse effects*; D005355:Fibrosis / Q000378:metabolism; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
chemical_list: D015314:Dialysis Solutions; D051785:Smad Proteins; D016211:Transforming Growth Factor alpha