学术论文

      PI3K/CTGF信号通路在TGF-β1诱导A549细胞表达collagenI过程中的作用

      Effects of PI3K/CTGF signaling pathway on TGF-β1-induced collagen I expression in A549 cells

      摘要:
      目的:研究磷脂酰肌醇3-激酶/结缔组织生长因子(PI3K/CTGF)信号通路在转化生长因子β1(TGF-β1)诱导人肺腺癌A549细胞表达I型胶原蛋白(collagen I)过程中的分子机制.方法:体外培养A549细胞,予TGF-β1刺激,观察CTGF和collagen I的mRNA和蛋白表达及PI3K信号通路的活化;PI3K抑制剂LY294002预先处理A549细胞后,观察TGF-β1刺激下CTGF和collagen I mRNA和蛋白表达的变化;CTGF特异性siRNA干扰A549细胞中CTGF的表达后,观察TGF-β1刺激下collagen I mRNA和蛋白表达的变化和PI3K信号通路的活化.结果:TGF-β1可以诱导A549细胞中CTGF和collagen I的mRNA和蛋白表达以及PI3K信号通路的活化;PI3K特异性抑制剂LY294002可以部分逆转TGF-β1诱导的A549细胞中CTGF和Collagen I mRNA和蛋白表达的升高.干扰CTGF可以降低TGF-β1诱导的A549细胞collagen I mRNA和蛋白表达,而不影响PI3K信号通路的活化.结论:CTGF是TGF-β1/PI3K信号通路调控的即刻早期反应效应蛋白,参与了TGF-β1诱导的A549细胞中collagen I表达.
      Abstract:
      AIM:To investigate the molecular mechanism of transforming growth factor β1/phosphatylinositol 3-kinase/connective tissue growth factor (TGF-β1/PI3K/CTGF) signaling pathway in the induction of collagen I expression in human lung adenocarcinoma A 549 cells.METHODS: The A549 cells were cultured in vitro and stimulated by TGF-β1.The expression of CTGF and collagen I at mRNA and protein levels as well as the activation of PI 3K was measured. The A549 cells were pre-treated with PI3K inhibitor LY294002, the expression of CTGF and collagen I at mRNA and pro-tein levels was measured upon TGF-β1 stimulation.Under the condition of CTGF interference by siRNA-CTGF, the expres-sion of collagen I at mRNA and protein levels as well as the activation of PI 3K by TGF-β1 stimulation was measured .RE-SULTS:TGF-β1 stimulated the expression of CTGF and collagen I at mRNA and protein levels as well as the activation of PI3K at a dose-and time-dependant manner .PI3K inhibitor LY294002 partly reversed TGF-β1-induced CTGF and collagen I expression .Interference of CTGF down-regulated TGF-β1-induced collagen I expression without the effect on the activa-tion of PI3K.CONCLUSION:PI3K signaling pathway plays a pivotal role in TGF-β1-induced collagen I expression in the A549 cells.CTGF is an immediate early response effector protein of TGF-β1/PI3K signaling pathway and synergizes with TGF-β1 in the induction of collagen I expression in the A 549 cells.
      作者单位: 温州医科大学附属第一医院呼吸与危重症医学科,浙江温州,325000
      刊 名: 中国病理生理杂志 ISTICPKU
      年,卷(期): 2017, 33(3)
      分类号: R730.23
      在线出版日期: 2017年4月10日
      基金项目: 国家自然科学基金资助项目