Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells.
Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells.
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Zeb1 是 Six2 在后肾间充质细胞增殖、凋亡和迁移中的潜在调节因子
DOI：
10.3390/ijms17081283
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发表时间：
2016-08-06
影响因子：
5.6
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Gu Y;Zhao Y;Zhou Y;Xie Y;Ju P;Long Y;Liu J;Ni D;Cao F;Lyu Z;Mao Z;Hao J;Li Y;Wan Q;Kanyomse Q;Liu Y;Ren D;Ning Y;Li X;Zhou Q;Li B
肾单位祖细胞围绕在输尿管芽尖（UB）周围，并与UB诱导相互作用以产生肾单位，肾功能的基本单位。这一过程是由肾单位祖细胞自我更新和消耗之间的内部平衡决定的，依赖于复杂的调控网络。已有报道Zeb 1调节小鼠胚胎间充质细胞的增殖。然而，Zeb 1在肾单位生成中的作用尚不清楚，特别是在后肾间充质（MM）中。本研究分别采用EdU法、流式细胞术法和创伤愈合法检测MM细胞的增殖、凋亡和迁移。同时采用Western和RT-PCR方法检测Zeb 1和Six 2在MM细胞和发育中肾脏中的表达水平。此外，利用双荧光素酶技术研究了Zeb 1和Six 2的分子关系。我们发现Zeb 1基因的敲低降低了MM细胞的增殖、迁移和促进细胞凋亡，而Zeb 1基因的过表达则导致相反的结果。Western-blot和RT-PCR结果显示，Zeb 1基因敲低可降低MM细胞中Six 2的表达，而Zeb 1基因过表达则相反。类似地，Zeb 1在荧光素酶测定中促进Six 2启动子报告活性。然而，与对照细胞相比，Zeb 1和Six 2的双敲低并没有增强MM细胞的凋亡。然而，Zeb 1和Six 2的双重沉默抑制了细胞增殖。此外，我们还发现Zeb 1和Six 2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Six 2和Zeb 1之间可能存在复杂的调控网络。总之，我们证明Zeb 1促进增殖和凋亡，并抑制MM细胞的迁移，与Six 2相关。
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.
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影响因子：
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作者：
Eldeeb MA;Fahlman RP
通讯作者：
Fahlman RP
影响因子：
3.7
作者：
McLaughlin, Nathan;Yao, Xiao;El-Dahr, Samir S.
通讯作者：
El-Dahr, Samir S.
影响因子：
2.2
作者：
Balhana, Ricardo;Stoker, Neil G.;Sikder, Mahmudul Hasan;Chauviac, Francois-Xavier;Kendall, Sharon L.
通讯作者：
Kendall, Sharon L.
影响因子：
4.8
作者：
Filios, Stephen R.;Xu, Guanlan;Shalev, Anath
通讯作者：
Shalev, Anath
DOI：
10.1016/j.bbrc.2016.02.036
发表时间：
2016-03-18
影响因子：
3.1
作者：
Guo, Shiguang;Mao, Li;Wang, Xiao-dong
通讯作者：
Wang, Xiao-dong