大鼠腹膜间皮细胞中转化生长因子β1对TNF-α表达的影响

目的 探讨在大鼠腹膜间皮细胞(RPMC)中转化生长因子β1 (TGF-β1)对肿瘤坏死因子-α (tumor necrosis factor-α,TNF-α)表达的影响及其机制.方法 在体外培养的大鼠腹膜间皮细胞模型中,加入TGF-β1(10ng/ml)预刺激,研究RPMC中肿瘤坏死因子-α(TNF-α)的表达；体外转染Smad7至RPMC后,研究其对TGF-β1(10 ng/ml)刺激后RPMCs中TNF-α和p38表达的影响.p38抑制剂SB203580(10umol/L)预处理RPMCs后,加入TGF-β1(10 ng/ml)刺激,研究抑制p38信号通路后对TNF-α表达的影响.结果 RT-PCR结果显示,与0h对照组相比,3h、6h、12hTGF-β1刺激组TNF-α表达明显增加(P＜0.05).上调表达Smad7抑制TGF-β1刺激RPMC产生TNF-α的作用,p38抑制剂SB203580亦能抑制TGF-β1刺激RPMC表达TNF-α的作用.TGF-β1参与p38磷酸化的活化,Smad7可抑制TGF-β1对它的激活反应；与正常对照组比较,TGF-β1刺激组磷酸化(p)-p38的表达显著增加(P＜0.05),与TGF-β1刺激组比较,Smad7治疗组p-p38的表达显著减弱(P＜0.05).结论 在大鼠腹膜间皮细胞中,TGF-β1能促进TNF-α的表达,其作用机制可能是依赖活化p38MAPK信号通路来实现的.

Effect of transforming growth factor-β1 on TNF-α expression in rat peritoneal mesothelial cells

Objective To observe the effect of transforming growth factor-β1（TGF-β1）on the expression of tumor necrosis factor-α（TNF-α） in rat peritoneal mesothelial cells（RPMCs） and its machanism.Method TGF-β1-induced RPMCs model in vitro was established,the expression of TNF-α in the TGF-β1-induced RPMCs was explored;the intervention of Smad7 on the expression of TNF-α and p38 signal proteins induced by TGF-β1 in RPMCs were observed,and the intervention of p38 inhibitor SB203580 on the expression of TNF-α induced by TGF-β1 in RPMCs was also observed.Results TGF-β1 could stimulate TNF-α expression in RPMCs;Compared with control group,TNF-α mRNA levels were significantly increased 3h,6h and 12h after treatment with TGF-β1（p0.05）..Over-expressed Smad7 could reduce the expression of TNF-α induced by TGF-β1（p0.01）,p38 inhibitor also could reduce the expression of TNF-α induced by TGFβ1（p0.01）.TGF-β1 could activate p38 signaling pathway,over-expressed Smad7 could inhibit this role of TGF-β1.Comparing with control group,the expression of p-p38 was increased in TGF-β1-stimulated-group;comparing with TGF-β1 stimulated-group,the expression of p-p38 was reduced in Smad7 gene transfer group.Conclusion TGF-β1 can stimulate the expression of TNF-α in rat peritoneal mesothelial cells,and this role is p38 MAPK dependent.