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

• Published in: The Journal of surgical research Vol. 154; no. 2; pp. 312 - 316
• Main Authors: Falk, Peter, B.Sc, Bergström, Maria, Ph.D., M.D, Palmgren, Ingrid, B.Sc, Holmdahl, Lena, Ph.D., M.D, Breimer, Michael E., Ph.D., M.D, Ivarsson, Marie-Louise, Ph.D., M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 15.06.2009
• Subjects: Biological and medical sciences; General aspects; Medical sciences; Surgery; fibrinolysis; peritoneum; experimental model; mesothelium; proliferation; adhesions; transforming growth factor β; fibrinolytic factors; mesothelial cells; Human; Cell proliferation; Mesothelium; Transforming growth factor β; Mesothelial cell; Experimental study; Adhesion; Fibrinolysis; In vitro; Medicine; Models; Transforming growth factor β1; Fibrinolytic; Peritoneum
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2008.05.012

Background Increased 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 methods Total 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. Results Total 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. Conclusions This 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.