Cell-shape-associated transcriptional activation of the p52(PAI-1) gene in rat kidney cells.
Cell-shape-associated transcriptional activation of the p52(PAI-1) gene in rat kidney cells.
复制标题
大鼠肾细胞中 p52（PAI-1）基因的细胞形状相关转录激活。
DOI：
10.1042/bj2881017
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Ahmed,A
中科院分区：
文献类型：
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作者：
Higgins,PJ;Ryan,MP;Ahmed,A
在正常大鼠肾（NRK）细胞中，细胞松弛素D（CD）可使纤溶酶原激活物抑制剂1型（p52（派-1））的从头合成和细胞外基质沉积增加10-22倍。从平坦到圆形表型的转变伴随着发生，并且实际上可能先于p52（派-1）诱导;形态学和p52（派-1）反应都是剂量依赖性的。增强的合成变得明显之间的4和5小时的治疗NRK细胞与100 μ M-CD，相关的过渡从25%到60%以上的圆形细胞。CD相关的p52（派-1）mRNA丰度和蛋白质生物合成的增加在连续CD暴露的6和8小时之间达到最大，此后下降了50%，但在24小时内仍保持升高（至少分别为对照值的6-21倍）。p52（派-1）mRNA丰度在这24小时点的变化反映了大约。5-p52（派-1）基因转录增加一倍。这些数据证实了先前的基于诱导反应的放线菌素D敏感性的建议[Higgins & Ryan（1992）Biochem.J.284，433-439]，即CD介导的p52（派-1）表达的增加至少部分是由于转录水平事件。由于CD还增强了对生长因子或细胞因子的特异性细胞应答，因此在存在和不存在血清生长因子的情况下，使用静止NRK细胞[不表达p52（派-1）的生长状态]作为模型系统，评价了该诱导剂的潜在有效性。CD刺激的静止NRK细胞中p52（派-1）的合成和基质沉积的诱导在生长因子缺乏的条件下是有效的，当CD同时加入血清。因此，CD单独是NRK细胞中p52（派-1）表达的完全诱导剂，这一观察结果支持细胞形状是p52（派-1）基因控制中的重要调控元件的论点。
The microfilament-disrupting agent cytochalasin D (CD) increased (by 10-22-fold) the synthesis de novo and extracellular matrix deposition of plasminogen-activator inhibitor type-1 [p52(PAI-1)] in normal rat kidney (NRK) cells. Transition from a flat to a round phenotype occurred concomitantly with, and may actually precede, p52(PAI-1) induction; both the morphological and p52(PAI-1) responses were dose-dependent. Augmented synthesis became evident between 4 and 5 h of treatment of NRK cells with 100 microM-CD, correlating with a transition from 25 to more than 60% rounded cells. CD-associated increases in p52(PAI-1) mRNA abundance and protein biosynthesis were maximal between 6 and 8 h of continuous CD exposure, declined by 50% thereafter, but remained elevated (by at least 6-21-fold respectively over control values) for 24 h. Changes in p52(PAI-1) mRNA abundance at this 24 h point reflected an approx. 5-fold increase in p52(PAI-1)-gene transcription. These data confirm previous suggestions, based on actinomycin D-sensitivity of the inductive response [Higgins & Ryan (1992) Biochem. J. 284, 433-439], that CD-mediated increases in p52(PAI-1) expression are at least partly due to transcription-level events. Since CD also augments specific cellular responses to growth factors or cytokines, the potential effectiveness of this inducer was evaluated both in the presence and absence of serum growth factors using quiescent NRK cells [a growth state in which p52(PAI-1) is not expressed] as a model system. Induction of p52(PAI-1) synthesis and matrix deposition in CD-stimulated quiescent NRK cells was as efficient under growth-factor-deficient conditions as when CD was added simultaneously with serum. CD alone is thus a complete inducer of p52(PAI-1) expression in NRK cells, an observation that supports the contention that cell shape is an important regulatory element in p52(PAI-1)-gene control.