title: Mast cell involvement in the progression of peritoneal fibrosis in rats with chronic renal failure.
abstract: OBJECTIVE
  Peritoneal fibrosis is a serious complication in patients with end stage renal disease (ESRD), especially those undergoing long-term peritoneal dialysis therapy. Since the peritoneum is a major site of mast cell accumulation, and since mast cells are known to facilitate the progression of organ fibrosis, they would also contribute to the pathogenesis of peritoneal fibrosis. The aim of this study was to reveal the involvement of mast cells in the progression of peritoneal fibrosis in chronic renal failure.
  
  
  METHODS
  Using a rat model with chronic renal failure (CRF) resulting from 5/6 nephrectomy, we examined the histopathological features of the rat peritoneum and compared them to those of age-matched sham-operated rat peritoneum. By treating the CRF rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of peritoneal fibrosis.
  
  
  RESULTS
  The CRF rat peritoneum was characterized by the wide staining of collagen III and an increased number of myofibroblasts, indicating the progression of fibrosis. Compared to sham-operated rat peritoneum, the number of toluidine blue-stained mast cells was significantly higher in the fibrotic peritoneum of CRF rats. The mRNA expression of fibroblast-activating factors and stem cell factor was significantly higher in peritoneal mast cells obtained from CRF rats than in those obtained from sham-operated rats. Treatment with tranilast significantly suppressed the progression of peritoneal fibrosis in CRF rats.
  
  
  CONCLUSIONS
  This study demonstrated for the first time that the number of mast cells was significantly increased in the fibrotic peritoneum of CRF rats. The proliferation of mast cells and their increased activity in the peritoneum were thought to be responsible for the progression of peritoneal fibrosis.
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.affiliation: Department of Physiology I, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Baba
authors.affiliation: Department of Anesthesiology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Department of Anesthesiology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Toyama
authors.affiliation: Department of Anesthesiology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ejima
authors.affiliation: Division of Molecular Medicine, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tachi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D010450:Endopeptidases; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D019899:Paracrine Communication; D056627:Peritoneal Fibrosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D024061:Collagen Type III; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D019089:Stem Cell Factor; D062367:ortho-Aminobenzoates; D000099167:Fibroblast Activation Protein Alpha; C012293:tranilast
keywords: chronic renal failure; fibroblast-activating factors; mast cells; peritoneal fibrosis; tranilast