title: Differential regulation of mesothelial cell fibrinolysis by transforming growth factor beta 1.
abstract: Inflammation and tissue trauma during the surgical procedure reduce the peritoneal fibrinolytic capacity. These conditions promote adhesion formation, and are associated with increased expression of transforming growth factor beta 1 (TGF-beta1). The objective of the present study was to investigate whether TGF-beta1 regulates the expression of fibrinolytic components in peritoneal mesothelial cells. Human peritoneal mesothelial cells (HPMC) were cultured and treated with various concentrations of human recombinant TGF-beta1 (0.1, 1.0 and 10 ng/mL) for 24 h. Levels of tissue- and urokinase plasminogen activator (t-PA and uPA), plasminogen activator inhibitor type-1 (PAI-1) and type-2 (PAI-2) mRNA and protein were assessed by quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) and ELISA, respectively. HPMC expressed these components at the gene and protein level. TGF-beta1 downregulated, dose-dependently t-PA mRNA and protein to about 50% of control values (p = 0.0010), and doubled PAI-1 protein production (p = 0.0008) compared to untreated controls. Although uPA gene expression increased in cells exposed to TGF-beta1, the corresponding protein concentration in conditioned media did not. PAI-2 was not affected, either at the gene or protein level. In conclusion, the results indicate that fibrinolytic capacity of mesothelial cells is reduced by TGF-beta1, suggesting that peritoneal adhesion formation induced by TGF-beta1 may be mediated, in part, through reduction in fibrin degradation capacity at an early stage of peritoneal tissue repair.
authors: Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
authors: P
authors: P
authors: Falk
authors: C
authors: C
authors: Ma
authors: N
authors: N
authors: Chegini
authors: L
authors: L
authors: Holmdahl
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects; D005342:Fibrinolysis / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D010529:Peritoneal Cavity / Q000473:pathology / Q000503:physiopathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator