title: Tissue factor and factor v involvement in rat peritoneal fibrosis.
abstract: OBJECTIVE
  Fibrin deposition on the peritoneum has been frequently observed in peritoneal fibrosis induced by long-term peritoneal dialysis. The present study was conducted to clarify the contribution of factor Xa through tissue factor and factor V expression in peritoneal fibrosis.
  
  
  METHODS
  Wistar rats were intraperitoneally injected with chlorhexidine gluconate (CG) every day. For the interventional study, the factor Xa inhibitor fondaparinux was subcutaneously administered. After 28 days of CG injection, peritoneal specimens were examined by immunohistochemical analyses and in situ hybridization.
  
  
  RESULTS
  The peritoneal submesothelial compact zone was observed to be markedly thicker in the CG-injected groups than in the normal group, and that thickness was dose dependent. Immunohistochemical study revealed massive fibrin, fibronectin, and type IV collagen depositions in the CG-injected groups, which was markedly higher than that in the normal group. Macrophage infiltration and staining for tissue factor, factor V, factor X, and protease-activated receptor-2 were intense in the CG-injected groups and negative/trace in the normal group. Tissue factor and factor V mRNAs were abundant in cells in the thickened peritoneum. A double-labeling experiment revealed that tissue factor was observed mainly in macrophages, and factor V was abundantly distributed in the fibrotic tissue together with macrophages. Fondaparinux treatment decreased the thickness of submesothelial fibrotic tissue, and size and number of CD31-positive vessels.
  
  
  CONCLUSIONS
  These results suggest that expression of tissue factor and factor V in infiltrated macrophages, together with factor X deposition, may progress angiogenesis and accumulation of extracellular matrix components, partly via profibrotic and procoagulant mechanisms in the peritoneum after inflammatory stimulation.
authors.affiliation: Division of Molecular Medicine, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Saito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitamoto
authors.forename: Kozue
authors.initials: K
authors.lastname: Kato
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Hisayo
authors.initials: H
authors.lastname: Kitamura
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Uemura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nogaki
authors.forename: Toshiya
authors.initials: T
authors.lastname: Takeda
authors.forename: Noriko
authors.initials: N
authors.lastname: Mori
authors.forename: Takahiko
authors.initials: T
authors.lastname: Ono
mesh_terms: D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005165:Factor V / Q000378:metabolism*; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors; D005355:Fibrosis; D000077425:Fondaparinux; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D065427:Factor Xa Inhibitors; D011134:Polysaccharides; D005165:Factor V; D013925:Thromboplastin; D015951:Factor Xa; D000077425:Fondaparinux; C010882:chlorhexidine gluconate; D002710:Chlorhexidine