Falk Peter, Bergström Maria, Palmgren Ingrid, Holmdahl Lena, Breimer Michael E, Ivarsson Marie-Louise
Fibrinolysis Laboratory/Tissue Centre, Department of Surgery, The Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
J Surg Res. 2009 Jun 15;154(2):312-6. doi: 10.1016/j.jss.2008.05.012. Epub 2008 Jun 20.
Increased transforming growth factor-beta (TGF-beta) levels are associated with fibrosis, affected cell proliferation, and postsurgical adhesion development, but the knowledge regarding TGF-beta response to the surgical trauma is limited. This study investigated TGF-beta(1-3) isoforms and fibrinolytical factors in peritoneal serosal fluid during abdominal surgery, together with the in vitro effect of TGF-beta(1-3) on human mesothelial cell proliferation.
Total as well as biologically active TGF-beta(1-3) 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-beta(1-3) stimulation was also investigated.
Total TGF-beta1 and TGF-beta2 levels were similar in serosal fluid and plasma while active fractions were increased in serosal fluid. In contrast, total fraction of TGF-beta3 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-beta(1-3) concentrations decreased cell proliferation, while lower concentrations of TGF-beta1 increased mesothelial cell proliferation.
This human study shows increased active TGF-beta levels in peritoneal serosal fluid, compared with plasma, during abdominal surgery and that TGF-beta1 at physiological concentrations increased human mesothelial cell proliferation in vitro. TGF-beta cytokines may be involved in postsurgical adhesion formation.
转化生长因子-β（TGF-β）水平升高与纤维化、细胞增殖受影响及术后粘连形成有关，但关于TGF-β对外科创伤反应的认识有限。本研究调查了腹部手术期间腹膜浆液中TGF-β（1 - 3）亚型和纤溶因子，以及TGF-β（1 - 3）对人腹膜间皮细胞增殖的体外影响。
检测了23例接受结直肠癌手术患者的浆液和血浆中总的以及生物活性的TGF-β（1 - 3）和纤溶因子：组织型纤溶酶原激活物（t-PA）、尿激酶型纤溶酶原激活物（uPA）和纤溶酶原激活物抑制剂-1（PAI-1）。还研究了TGF-β（1 - 3）刺激后人原代腹膜间皮细胞培养物的体外增殖情况。
浆液和血浆中总的TGF-β1和TGF-β2水平相似，而浆液中活性部分增加。相比之下，浆液中TGF-β3的总部分高于血浆，而活性部分水平无差异。与血浆相比，浆液中纤溶酶原激活物（t-PA、uPA）升高而抑制剂（PAI-1）降低。体外腹膜间皮细胞增殖研究表明，高浓度的TGF-β（1 - 3）降低细胞增殖，而低浓度的TGF-β1增加腹膜间皮细胞增殖。
这项人体研究表明，腹部手术期间腹膜浆液中活性TGF-β水平高于血浆，且生理浓度的TGF-β1在体外增加人腹膜间皮细胞增殖。TGF-β细胞因子可能参与术后粘连形成。
