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。