title: Modulation of fibrinolytic system components in mesothelial cells by hyaluronan.
abstract: OBJECTIVE
  Hyaluronan (HA) is an important extracellular matrix component and is involved in fluid homeostasis, tissue repair, and response to infections. Previous studies have shown that supplementation of dialysis fluid with high molecular weight HA may have a positive impact on peritoneal solute and fluid transport characteristics. In the present study, we investigated the impact of HA on the synthesis of tissue-type plasminogen activator (t-PA) and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1) in cultured human peritoneal mesothelial cells (MC).
  
  
  METHODS
  Cultured human peritoneal MC isolated from omental tissue were used for the experiments. Concentrations of t-PA and PAI-1 antigens were measured in conditioned media of confluent MC using ELISA. Northern blot analysis was performed to investigate mRNA expression of t-PA, PAI-1, and low-density lipoprotein receptor-related protein.
  
  
  RESULTS
  Hyaluronan in a concentration as suggested for supplementation of dialysis fluid (10 mg/dL) did not have a significant impact on the synthesis of t-PA or PAI-1 in human MC. However, incubation of MC with higher concentrations of HA (30-1000 mg/dL) resulted in a concentration- and time- (8- 48 hours) dependent decrease in t-PA antigen release and mRNA expression. In contrast, PAI-1 antigen secretion was distinctly but not significantly increased in the presence of HA.
  
  
  CONCLUSIONS
  The expression of t-PA and PAI-1 in MC was not affected by low concentrations of HA. Therefore, it is reasonable to assume that supplementation of dialysis fluid with HA (10 mg/dL) will not decrease mesothelial fibrinolytic activity. Only high concentrations (> 50 mg/dL) may disturb the balance between intraperitoneal generation and degradation of fibrin by decreasing t-PA synthesis.
authors.affiliation: Department of Nephrology, Medizinische Klinik, Innenstadt, Klinikum der Universität München, Germany. tsitter@medinn.med.uni-muenchen.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Sitter
authors.forename: Matthias
authors.initials: M
authors.lastname: Sauter
authors.forename: Bettina
authors.initials: B
authors.lastname: Haslinger
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D009852:Omentum / Q000187:drug effects / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
chemical_list: D000276:Adjuvants, Immunologic; D017395:Plasminogen Activator Inhibitor 1; D006820:Hyaluronic Acid; D010959:Tissue Plasminogen Activator