Studies of TGF-β1-3 in Serosal Fluid During Abdominal Surgery and Their Effect on In Vitro Human Mesothelial Cell Proliferation

BackgroundIncreased transforming growth factor-β (TGF-β) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-β response to the surgical trauma is limited. This study investigated TGF-β1-3 isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-β1-3 on human mesothelial cell proliferation.Materials and methodsTotal as well as biologically active TGF-β1-3 and fibrinolytic factors: t-PA, uPA, and PAI-1 were measured in serosal fluid and plasma from 23 patients undergoing colorectal cancer surgery. In vitro proliferation of human primary mesothelial cell cultures upon TGF-β1-3 stimulation was also investigated.ResultsTotal TGF-β1 and TGF-β2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-β3 was higher in serosal fluid compared with plasma, while levels of active fractions did not differ. Plasminogen activators (t-PA, uPA) were elevated while the inhibitor (PAI-1) was decreased in serosal fluid compared with plasma. The in vitro mesothelial cell proliferation studies revealed that high TGF-β1-3 concentrations decreased cell proliferation, while lower concentrations of TGF-β1 increased mesothelial cell proliferation.ConclusionsThis human study shows increased active TGF-β levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-β1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-β cytokines may be involved in postsurgical adhesion formation.