IFNγ影响肝星状细胞α_1(Ⅰ)mRNA表达信号的传递途径

IFNγ affects collagen α_1(Ⅰ) mRNA gene expression signals transduction pathway in rat hepatic stellate cells

目的 :探明G蛋白在γ -干扰素诱导抑制胶原基因表达中发挥的作用 .方法 :通过活化的G蛋白及细胞内主要信号传递途径确定IFNγ诱导肝星状细胞 (HSC)α1(Ⅰ )mR NA表达的影响 .结果 :与对照比较IFNγ显著降低HSCα1(Ⅰ )胶原mRNA水平 (5 6 .7± 0 .3) % (P <0 .0 1) ;百日咳毒素 (PTX)可阻断IFNγ对α1(Ⅰ )mRNA水平的抑制作用 ,当为 10 μg·L-1时 ,α1(Ⅰ )mRNA水平提高到 (12 1± 16 ) %(P <0 .0 1) ,但对阻断cAMP或PKA没有抑制作用 .结论 :IFNγ抑制HSCα1(Ⅰ )胶原mRNA表达受PTX敏感的G蛋白调节 .

AIM: To investigate the role of G protein in IFNγ induced inhibition of collagen gene expression. METHODS: Effect of IFNγ on collagen α1(Ⅰ) messenger RNA (mRNA) level was measured in cultured hepatic stellate cells in basal condition and after inhibiting or activating G protein, and principal pathway of intracellular signal transduction. RESULTS: IFNγ significantly decreased the level of α1(Ⅰ) collagen mRNA(56.7±0.3)% of control ( P <0.01). Treatment of cells with pertussis toxin inhibited this effect, the level of α1 (Ⅰ) collagen mRNA up to (121± 16)% of control ( P <0.01),whereas blocking adenylate cyclase or protein kinase (PKA) had no effect. CONCLUSION: IFNγ induced inhibition of α1(Ⅰ) collagen gene expression in hepatic stellate cells may be mediated by a pertussis toxin sensitive G protein.