GD1a对基质金属蛋白酶-9在不同细胞类型中表达的调控作用

Diverse effects of ganglioside GD1a on MMP-9 regulation in different species of cells

目的在不同的细胞类型中,检测神经节苷脂GD1a是否抑制基质金属蛋白酶-9(MMP-9)的表达。方法采用逆转录PCR法和酶谱法检测MMP-9及MMP-2的表达。结果在鼠黑色素瘤B16细胞中,神经节苷脂GD1a促进MMP-9的表达,而在小鼠肺癌Lewis细胞、人单核细胞THP-1及人子宫颈癌HeLa细胞中,神经节苷脂GD1a降低MMP-9的表达。在上述细胞中,神经节苷脂GD1a不影响基质金属蛋白酶MMP-2的表达;肿瘤坏死因子TNF-α在这几种细胞中均能促进MMP-9的表达,但对MMP-2无影响;在B16细胞中,GD1a通过胞窖膜介导信号传递,并且主要通过ERK促进MMP-9的表达,而在Lewis细胞中,GD1a不通过胞窖膜介导信号传递,但部分通过p38、ERK和JNK抑制MMP-9表达。结论在不同的细胞类型中,神经节苷脂GD1a能够激活不同的信号转导途径。

Objective To determine if GD1a suppresses MMP-9 expression in every cell type. Methods The expression of MMP-9 and MMP-2 was determined by RT-PCR and by zymography. Results In mouse mela- noma B 16 cells, ganglioside GD1 a induced the expression of MMP-9. However, in mouse lung cancer Lewis cells,human monocyte THP-1 cells and human carcinoma cervicis HeLa cells, ganglioside GD1a suppressed the expression of MMP-9. In mouse lung cancer Lewis cells and human monocyte THP-1 cells,GD1a also decreased the activity of MMP-9. In these cells, ganglioside GD1 a had no effects on the expression of MMP- 2. TNF-α increased the expression of MMP-9 but not MMP-2. In B16 cells, GD1 a signals are mediated partly through caveolae, and mainly through ERK for inducing of MMP-9 expression;while in Lewis cells, GD1 a signals are not mediated through caveolae, but partly through p38, ERK and JNK. Conclusion Ganglioside GD1a activates different signal pathways in different cell types.