Falk P, Ma C, Chegini N, Holmdahl L
Department of Surgery, Sahlgrenska University Hospital/Ostra, Göteborg University, Sweden.
Scand J Clin Lab Invest. 2000 Oct;60(6):439-47. doi: 10.1080/003655100448419.
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.
手术过程中的炎症和组织创伤会降低腹膜的纤维蛋白溶解能力。这些情况会促进粘连形成，并与转化生长因子β1（TGF-β1）表达增加有关。本研究的目的是调查TGF-β1是否调节腹膜间皮细胞中纤维蛋白溶解成分的表达。培养人腹膜间皮细胞（HPMC），并用不同浓度的人重组TGF-β1（0.1、1.0和10 ng/mL）处理24小时。分别通过定量逆转录聚合酶链反应（Q-RT-PCR）和酶联免疫吸附测定（ELISA）评估组织型纤溶酶原激活物和尿激酶型纤溶酶原激活物（t-PA和uPA）、纤溶酶原激活物抑制剂1型（PAI-1）和2型（PAI-2）的mRNA和蛋白质水平。HPMC在基因和蛋白质水平表达这些成分。与未处理的对照相比，TGF-β1剂量依赖性地下调t-PA mRNA和蛋白质至对照值的约50%（p = 0.0010），并使PAI-1蛋白质产量增加一倍（p = 0.0008）。虽然暴露于TGF-β1的细胞中uPA基因表达增加，但条件培养基中的相应蛋白质浓度没有增加。PAI-2在基因或蛋白质水平均未受影响。总之，结果表明TGF-β1降低了间皮细胞的纤维蛋白溶解能力，提示TGF-β1诱导的腹膜粘连形成可能部分是通过在腹膜组织修复早期降低纤维蛋白降解能力介导的。
