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Upregulation of transcription factors in lung in the early phase of postpneumonectomy lung growth.

机译:肺切除术后肺生长早期肺中转录因子的上调。

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In the adult rodent, pneumonectomy results in compensatory lung growth characterized by cell proliferation. The molecular mechanisms governing this response remain unknown. We hypothesized that, in the early period postpneumonectomy, upregulated expression of transcription factors drives the growth process. We utilized a cDNA expression array to screen for upregulated transcription factors after left pneumonectomy in adult C57BL/6 mice, using unoperated mice as controls. Quantification of mRNA expression in the remaining lung at 2 h demonstrated a twofold or greater upregulation of six transcription factors: early growth response gene-1 (Egr-1), Nurr77, tristetraprolin, the primary inhibitor of nuclear factor-kappa B (I kappa B-alpha), gut-enriched Kruppel-like factor (GKLF), and LRG-21. Northern analysis was used to quantify the upregulation of expression of these genes relative to sham thoracotomy and unoperated controls. The largest increase was in Egr-1 (4.7-fold > naive). Time-course analysis overthe first 24 h confirmed the transient nature of the early upregulation. In the context that postpneumonectomy lung growth is associated with cell proliferation and that genes such as Egr-1, Nurr77, LRG-21, and tristetraprolin have known roles in stress response, vascular biology, embryology, and cellular development, these data support the concept that transcription factors function early in the cascade of events leading to the compensatory response.
机译:在成年啮齿动物中,肺切除术导致以细胞增殖为特征的代偿性肺生长。控制这种反应的分子机制仍然未知。我们假设在肺切除术后的早期,转录因子的表达上调驱动了生长过程。我们利用cDNA表达阵列筛选成年C57BL / 6小鼠左肺切除后使用未手术小鼠作为对照的上调转录因子。在剩余的2小时肺中mRNA表达的定量显示六个转录因子的两倍以上的上调:早期生长反应基因1(Egr-1),Nurr77,tristetraprolin,核因子kappa B(I kappa的主要抑制剂) B-alpha),富含肠道的Kruppel样因子(GKLF)和LRG-21。相对于假手术和未手术的对照,使用Northern分析来量化这些基因表达的上调。增幅最大的是Egr-1(4.7倍>天真)。前24小时的时程分析证实了早期上调的短暂性质。在肺切除术后肺生长与细胞增殖有关的背景下,Egr-1,Nurr77,LRG-21和tristetraprolin等基因在应激反应,血管生物学,胚胎学和细胞发育中具有已知作用,这些数据支持了这一概念。转录因子在导致代偿性反应的一系列事件的早期起作用。

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