title: Involvement of TGF-beta signal for peritoneal sclerosing in continuous ambulatory peritoneal dialysis.
abstract: BACKGROUND
  Functional failure of the peritoneal membrane is the most serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD). Transforming growth factor-beta (TGF-ss) is one of the key mediators of fibrosis in some organs, and is thought to be involved in peritoneal alterations. In this study, we examined the role of TGF-beta1/TGF-ss receptors for human peritoneal mesothelial cells (HPMCs) and fibroblasts, and their interactions in CAPD patients.
  
  
  METHODS
  HPMCs were cultured for 48 h in a medium containing normal- dose glucose (7 mM), high-dose glucose (30 mM) and mannitol as an osmotic agent, equal to 30 mM glucose. Cell proliferation was observed using the Tetra Color One assay. The concentration of TGF-beta1 in culture supernatants was measured by enzyme-linked immunosorbent assay (ELISA). The expression of TGF-ss receptor types I and II was observed by flow cytometry. HPMCs and fibroblasts were co-cultured and assayed using transwell inserts in order to identify the effects of the high-concentration glucose solution.
  
  
  RESULTS
  HPMC proliferation was inhibited by the high concentration of glucose but not by mannitol. The inhibition was abrogated by the neutralizing antibody for TGF-beta1. TGF-beta1 was induced by a high concentration of glucose but not by mannitol. The expression of both TGF-ss receptors was augmented in culture with the high concentration of glucose but not with mannitol. In the co-culture assay, the number of HPMCs was decreased and fibroblasts were significantly increased in culture with the high concentration of glucose.
  
  
  CONCLUSIONS
  A high concentration of glucose induced a large amount of TGF-beta1 and enhanced the expression of TGF-ss receptors. HPMCs were sensitive to TGF-beta1 in response to a high concentration of glucose. These data suggest that TGF-beta1 from HPMCs exposed to a high concentration of glucose down-regulates the proliferation of HPMCs and accelerates peritoneal fibrosis.
authors.affiliation: Department of Internal Medicine, Division of Hematology, Nephrology and Rheumatology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Naiki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.forename: Koki
authors.initials: K
authors.lastname: Matsuo
authors.forename: Satoru
authors.initials: S
authors.lastname: Yonekawa
authors.forename: Mika
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Akihisa
authors.initials: A
authors.lastname: Kanamaru
mesh_terms: D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010537:Peritoneum / Q000166:cytology* / Q000473:pathology*; D011336:Probability; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D012598:Sclerosis / Q000209:etiology; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D005947:Glucose