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Int. J. Mol. Sci. 2016, 17(9), 1504;

Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis

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
The fifth Clinical College of Medicine, Chongqing Medical University, Chongqing 400016, China
Department of Laboratory Medicine, the First Hospital of Xi’an, Xi’an 710002, China
Department of scientific and technological activity, Chongqing Yucai Middle School, Chongqing 400016, China
Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing 400016, China
Author to whom correspondence should be addressed.
Academic Editor: Nick Hadjiliadis
Received: 3 May 2016 / Revised: 16 August 2016 / Accepted: 1 September 2016 / Published: 8 September 2016
(This article belongs to the Section Bioinorganic Chemistry)
View Full-Text   |   Download PDF [6045 KB, uploaded 8 September 2016]   |  


The metanephric mesenchyme (MM) cells are a subset of kidney progenitor cells and play an essential role in mesenchymal-epithelial transition (MET), the key step of nephron generation. Six2, a biological marker related to Wnt signaling pathway, promotes the proliferation, inhibits the apoptosis and maintains the un-differentiation of MM cells. Besides, LiCl is an activator of Wnt signaling pathway. However, the role of LiCl in cellular regulation of MM cells remains unclear, and the relationship between LiCl and Six2 in this process is also little known. Here, we performed EdU assay and flow cytometry assay to, respectively, detect the proliferation and apoptosis of MM cells treated with LiCl of increasing dosages. In addition, reverse transcription-PCR (RT-PCR) and Western-blot were conducted to measure the expression of Six2 and some maker genes of Wnt and bone-morphogenetic-protein (BMP) signaling pathway. Furthermore, luciferase assay was also carried out to detect the transcriptional regulation of Six2. Then we found LiCl promoted MM cell proliferation at low-concentration (10, 20, 30, and 40 mM). The expression of Six2 was dose-dependently increased in low-concentration (10, 20, 30, and 40 mM) at both mRNA and protein level. In addition, both of cell proliferation and Six2 expression in MM cells declined when dosage reached high-concentration (50 mM). However, Six2 knock-down converted the proliferation reduction at 50 mM. Furthermore, Six2 deficiency increased the apoptosis of MM cells, compared with negative control cells at relative LiCl concentration. However, the abnormal rise of apoptosis at 30 mM of LiCl concentration implies that it might be the reduction of GSK3β that increased cell apoptosis. Together, these demonstrate that LiCl can induce the proliferation and apoptosis of MM cells coordinating with Six2. View Full-Text
Keywords: LiCl; metanephric mesenchyme cells; cell proliferation; cell apoptosis; Six2 LiCl; metanephric mesenchyme cells; cell proliferation; cell apoptosis; Six2

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Liu, J.; Ju, P.; Zhou, Y.; Zhao, Y.; Xie, Y.; Long, Y.; Gu, Y.; Ni, D.; Lyv, Z.; Mao, Z.; Hao, J.; Li, Y.; Wan, Q.; Kanyomse, Q.; Liu, Y.; Xiang, Y.; Wang, R.; Chen, X.; Zhang, J.; Liu, X.; Zhao, H.; Zhou, Q.; Li, G. Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis. Int. J. Mol. Sci. 2016, 17, 1504.

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