IGF-Ⅰ对体外培养的胎鼠肺成纤维细胞collagenⅠ合成的作用及其细胞内信号转导机制

Effect of insulin-like growth factor I on synthesis of collagen I in fetal rat lung fibroblasts in vitro and its intracellular signal transduction pathway

目的探讨IGF-Ⅰ对体外培养的胎鼠肺成纤维细胞collagenⅠ合成的作用及其细胞内的信号转导机制。方法体外培养胎鼠肺成纤维细胞,给予不同剂量的rhIGF-Ⅰ,作用不同的时间,研究rhIGF-Ⅰ对胎鼠肺成纤维细胞collagenⅠ合成的量效和时效作用,并通过用MEK1途径的特异性阻断剂PD98059或PI3K途径的特异性阻断剂LY294002预处理胎鼠肺成纤维细胞,研究rhIGF-Ⅰ刺激胎鼠肺成纤维细胞collagenⅠ合成的细胞内信号转导机制。结果 rhIGF-Ⅰ在10～200 ng/mL剂量作用下能剂量依赖性地刺激胎鼠肺成纤维细胞collagenⅠ mRNA的合成;rhIGF-Ⅰ在200 ng/mL时分别作用于胎鼠肺成纤维细胞0.5～24 h能时间依赖性地刺激collagenⅠ mRNA的合成;LY294002能部分抑制rhIGF-Ⅰ的促胎鼠肺成纤维细胞collagenⅠ mRNA合成的作用,PD98059对rhIGF-I促胎鼠肺成纤维细胞collagenⅠ mRNA合成的作用无影响。结论 IGF-Ⅰ是影响胎鼠肺成纤维细胞collagenⅠ合成的生长因子之一,rhIGF-Ⅰ促胎鼠肺成纤维细胞collagenⅠ合成的作用是通过PI3K-Akt途径实现的。

【Objective】 To study the effect of insulin-like growth factor Ⅰ on the synthesis of collagen-Ⅰ in fetal rat lung fibroblasts in vitro and its intracellular signal transduction pathway.【Methods】 Fetal rat lung fibroblasts were treated with rhIGF-Ⅰ（0～500 ng/mL） for 24 h and rhIGF-Ⅰ（200 ng/mL） for 0.5 h,1 h,2 h,6 h,12 h,24 h,48 h and 72 h to test the synthesis of collagen Ⅰ mRNA.Fetal rat lung fibroblasts were pretreated with MEK1 specific inhibitor PD98059 or PI3K specific inhibitor LY294002 to study the intracellular signal transduction pathway.【Results】 rhIGF-Ⅰ（10～200 ng/mL） increased collagen Ⅰ mRNA in fetal rat lung fibroblasts in a dose-dependent manner.rhIGF-Ⅰ（200 ng/mL for 0.5 h,1 h,2 h,6 h,12 h and 24 h） increased collagen Ⅰ mRNA in fetal rat lung fibroblasts in a time-dependent manner.LY294002 can partly block the rhIGF-Ⅰ-dependent increase in collagen Ⅰ mRNA,but PD98059 had no effect.【Conclusions】 IGF-Ⅰ is one of the most important growth factors involved in the synthesis of collagenⅠ.rhIGF-Ⅰ increases collagenⅠ synthesis in fetal rat lung fibroblasts by way of PI3K-Akt pathway.