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首页> 外文期刊>International Journal of Molecular Sciences >Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells
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Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells

机译：Zeb1是Sex2的潜在调节剂，在后肾间充质细胞的增殖，凋亡和迁移中。

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Nephron progenitor cells surround around the ureteric bud tips (UB) and inductively interact with the UB to originate nephrons, the basic units of renal function. This process is determined by the internal balance between self-renewal and consumption of the nephron progenitor cells, which is depending on the complicated regulation networks. It has been reported that Zeb1 regulates the proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in nephrons generation is not clear, especially in metanephric mesenchyme (MM). Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU assay, flow cytometry assay and wound healing assay, respectively. Meanwhile, Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in MM cells and developing kidney. Besides, the dual-luciferase assay was conducted to study the molecular relationship between Zeb1 and Six2 . We found that knock-down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in MM cells and Zeb1 overexpression contributed to the opposite results. Similarly, Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However, double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells compared with control cells. Nevertheless, double silence of Zeb1 and Six2 repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had an identical pattern in distinct developing phases of embryonic kidney. These results indicated that there may exist a complicated regulation network between Six2 and Zeb1 . Together, we demonstrate Zeb1 promotes proliferation and apoptosis and inhibits the migration of MM cells, in association with Six2 .
机译：肾单位祖细胞围绕输尿管芽尖（UB）周围，并与UB诱导相互作用，以产生肾单位，即肾功能的基本单位。该过程取决于肾单位祖细胞自我更新和消耗之间的内部平衡，这取决于复杂的调控网络。据报道，Zeb1调节小鼠胚胎中的间充质细胞的增殖。但是，Zeb1在肾单位生成中的作用尚不清楚，尤其是在后肾间质（MM）中。在这里，我们分别通过EdU测定，流式细胞术测定和伤口愈合测定检测了MM细胞的细胞增殖，凋亡和迁移。同时，用Western和RT-PCR检测Zeb1和Six2在MM细胞和发育中的肾脏中的表达水平。此外，进行了双荧光素酶分析以研究Zeb1和Six2之间的分子关系。我们发现敲低Zeb1减少MM细胞的细胞增殖，迁移和促进细胞凋亡，而Zeb1过表达导致相反的数据。 Western印迹和RT-PCR结果表明，敲除Zeb1会降低MM细胞中Six2的表达，而Zeb1的过表达则导致相反的结果。同样，Zeb1在萤光素酶测定中促进了Six2启动子报告基因活性。然而，与对照细胞相比，Zeb1和Six2的双重敲低并未增强MM细胞的凋亡。然而，Zeb1和Six2的双重沉默抑制了细胞增殖。此外，我们还发现Zeb1和Six2在胚胎肾脏的不同发育阶段具有相同的模式。这些结果表明，Six2和Zeb1之间可能存在复杂的调控网络。在一起，我们证明Zeb1与Six2相关联促进增殖和凋亡并抑制MM细胞的迁移。

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