title: Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and Migration of Metanephric Mesenchyme Cells.
abstract: 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.
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. littlebottlesky@gmail.com.
authors: Yuping
authors: Y
authors: Gu
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. xianzhaoya@gmail.com.|Department of Laboratory Medicine, The First Hospital of Xi'an, Xi'an 710002, China. xianzhaoya@gmail.com.
authors: Ya
authors: Y
authors: Zhao
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhouyuru93@gmail.com.|Undergraduates Class of 2012 Entry, The Fifth Clinical College of Medicine, Chongqing Medical University, Chongqing 400016, China. zhouyuru93@gmail.com.
authors: Yuru
authors: Y
authors: Zhou
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. yjxie@genetics.ac.cn.
authors: Yajun
authors: Y
authors: Xie
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. 18883936591@163.com.
authors: Pan
authors: P
authors: Ju
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. longyaoshui@gmail.com.
authors: Yaoshui
authors: Y
authors: Long
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. liujianingb@gmail.com.
authors: Jianing
authors: J
authors: Liu
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. dongshengni@outlook.com.
authors: Dongsheng
authors: D
authors: Ni
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. caofen7@gmail.com.
authors: Fen
authors: F
authors: Cao
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhongshilyu@gmail.com.
authors: Zhongshi
authors: Z
authors: Lyu
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. maozhaomin8@gmail.com.
authors: Zhaomin
authors: Z
authors: Mao
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. lanyxiu@163.com.
authors: Jin
authors: J
authors: Hao
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. liyimanb@gmail.com.
authors: Yiman
authors: Y
authors: Li
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. qy.wan@Outlook.com.
authors: Qianya
authors: Q
authors: Wan
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. quistmansa@gmail.com.
authors: Quist
authors: Q
authors: Kanyomse
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. liuyamin2013@126.com.
authors: Yamin
authors: Y
authors: Liu
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. rendielittle@gmail.com.
authors: Die
authors: D
authors: Ren
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. ningyating@outlook.com.
authors: Yating
authors: Y
authors: Ning
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. happylena18@gmail.com.
authors: Xiaofeng
authors: X
authors: Li
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhouqin@cqmu.edu.cn.
authors: Qin
authors: Q
authors: Zhou
authors: Division of Molecular Nephrology and The Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Clinical Diagnostics, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. libing@cqmu.edu.cn.|The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. libing@cqmu.edu.cn.
authors: Bing
authors: B
authors: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D002465:Cell Movement; D049109:Cell Proliferation; D017124:Conserved Sequence; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000254:growth & development; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C497420:Six2 protein, mouse; D014157:Transcription Factors; C519422:ZEB1 protein, mouse; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: Six2; Zeb1; cell apoptosis; cell migration; cell proliferation; metanephric mesenchyme cells