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首页> 外文期刊>Molecular and Cellular Biology >Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor.
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Regulation of urokinase-type plasminogen activator gene transcription by macrophage colony-stimulating factor.

机译：巨噬细胞集落刺激因子调节尿激酶型纤溶酶原激活物基因转录。

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The mouse urokinase-type plasminogen activator (uPA) gene was used as a model macrophage colony-stimulating factor 1 (CSF-1)-inducible gene to investigate CSF-1 signalling pathways. Nuclear run-on analysis showed that induction of uPA mRNA by CSF-1 and phorbol myristate acetate (PMA) was at the transcriptional level in bone marrow-derived macrophages. CSF-1 and PMA synergized strongly in the induction of uPA mRNA, showing that at least some components of CSF-1 action are mediated independently of protein kinase C. Promoter targets of CSF-1 signalling were investigated with NIH 3T3 cells expressing the human CSF-1 receptor (c-fms). uPA mRNA was induced in these cells by treatment with CSF-1, and a PEA3/AP-1 element at -2.4 kb in the uPA promoter was involved in this response. Ets transcription factors can act through PEA3 sequences, and the involvement of Ets factors in the induction of uPA was confirmed by use of a dominant negative Ets-2 factor. Expression of the DNA binding domain of Ets-2 fused to the lacZ gene product prevented CSF-1-mediated induction of uPA mRNA in NIH 3T3 cells expressing the CSF-1 receptor. Examination of ets-2 mRNA expression in macrophages showed that it was also induced synergistically by CSF-1 and PMA. In the macrophage cell line RAW264, the uPA PEA3/AP-1 element mediated a response to both PMA and cotransfected Ets-2. uPA promoter constructs were induced 60- to 130-fold by Ets-2 expression, and the recombinant Ets-2 DNA binding domain was able to bind to the uPA PEA3/AP-1 element. This work is consistent with a proposed pathway for CSF-1 signalling involving sequential activation of fms, ras, and Ets factors.
机译：小鼠尿激酶型纤溶酶原激活物（uPA）基因被用作模型巨噬细胞集落刺激因子1（CSF-1）诱导基因，以研究CSF-1信号通路。核运行分析表明，CSF-1和佛波醇肉豆蔻酸酯乙酸盐（PMA）对uPA mRNA的诱导在骨髓来源的巨噬细胞中处于转录水平。 CSF-1和PMA在uPA mRNA的诱导中具有强大的协同作用，表明CSF-1作用的至少某些成分独立于蛋白激酶C介导。用表达人CSF的NIH 3T3细胞研究了CSF-1信号的启动子靶点-1受体（c-fms）。通过用CSF-1处理在这些细胞中诱导uPA mRNA，并且uPA启动子中-2.4 kb处的PEA3 / AP-1元件参与了该反应。 Ets转录因子可以通过PEA3序列起作用，并且通过使用显性负Ets-2因子证实了Ets因子参与了uPA的诱导。与lacZ基因产物融合的Ets-2的DNA结合结构域的表达阻止了表达CSF-1受体的NIH 3T3细胞中CSF-1介导的uPA mRNA的诱导。检查巨噬细胞中的ets-2 mRNA表达表明，它还被CSF-1和PMA协同诱导。在巨噬细胞系RAW264中，uPA PEA3 / AP-1元件介导了对PMA和共转染的Ets-2的响应。通过Ets-2表达将uPA启动子构建体诱导60到130倍，并且重组Ets-2 DNA结合结构域能够结合uPA PEA3 / AP-1元件。这项工作与CSF-1信号传导的拟议途径一致，该途径涉及fms，ras和Ets因子的顺序激活。

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