title: Peritoneal morphological and functional changes associated with platelet-derived growth factor B.
abstract: BACKGROUND
  Morphological changes associated with long-term peritoneal dialysis (PD) include increased vascular surface area due to angiogenesis, submesothelial fibrosis and epithelial mesenchymal transition. Platelet-derived growth factor (PDGF) has been associated with all of these phenomena, and is a prototypical 'response to injury' growth factor.
  
  
  METHODS
  Rats received an intraperitoneal injection of adenoviral vector expressing PDGF-B. At sacrifice, we analysed the structure and function of the peritoneal membrane. Gene expression in the peritoneal tissue was assessed for changes suggestive of epithelial mesenchymal transition.
  
  
  RESULTS
  Over-expression of PDGF in the rat peritoneum led to significant angiogenesis, cellular proliferation and submesothelial thickening. Although PDGF induced expression of transforming growth factor beta, there was a lack of activation of this growth factor, and we believe that this explains the lack of significant collagen accumulation observed by a hydroxyproline assay. Despite evidence of angiogenesis and subsequent increased solute transport, we observed only a transient, non-significant impact on ultrafiltration function. This suggests that increased vascular surface area is necessary, but not sufficient, to produce ultrafiltration dysfunction. There was no evidence of epithelial mesenchymal transition observed either in regulation of associated genes such as Snail or E-Cadherin or in the lack of dual-labelled epithelial and mesenchymal cells on immunofluorescence. Mesothelial cells exposed to PDGF-B demonstrated increased collagen gene expression.
  
  
  CONCLUSIONS
  PDGF-B induced angiogenesis without fibrosis in the peritoneum. The lack of significant ultrafiltration dysfunction and epithelial mesenchymal transition, as observed in patients on PD, suggests that PDGF-B may play a role, but is not the integral component, in response to peritoneal injury.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Davide
authors.initials: D
authors.lastname: Cina
authors.forename: Pranali
authors.initials: P
authors.lastname: Patel
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Bethune
authors.forename: Jessica
authors.initials: J
authors.lastname: Thoma
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Rodriguez-Lecompte
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hoff
authors.forename: Limin
authors.initials: L
authors.lastname: Liu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Margetts
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D003094:Collagen / Q000235:genetics; D024042:Collagen Type I; D004848:Epithelium / Q000473:pathology; D015870:Gene Expression; D020571:Genes, sis; D005822:Genetic Vectors; D006801:Humans; D008648:Mesoderm / Q000473:pathology; D009389:Neovascularization, Pathologic; D010530:Peritoneal Dialysis / Q000009:adverse effects; D010537:Peritoneum / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D017395:Plasminogen Activator Inhibitor 1; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D003094:Collagen