Nanog down-regulates the Wnt signaling pathway via β-catenin phosphorylation during epidermal stem cell proliferation and differentiation.
Nanog down-regulates the Wnt signaling pathway via β-catenin phosphorylation during epidermal stem cell proliferation and differentiation.
复制标题
Nanog在表皮干细胞增殖和分化过程中通过β-catenin磷酸化下调Wnt信号通路。
DOI：
10.1186/2045-3701-5-5
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发表时间：
2015
影响因子：
7.5
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Cheng P;Sun X;Yin D;Xu F;Yang K;Qin L;Dong Y;Guo F;Chen A;Zhang W;Huang H
皮肤组织的稳态是由表皮干细胞（EpSCs）的增殖和分化之间的平衡维持的。EpSC的增殖和分化是一个复杂的过程，受多种因素和信号通路的调控。本研究旨在探讨Nanog与Wnt/β-catenin通路在EpSCs增殖分化中的关系。我们的研究结果表明，在研究期间，EpSC在神经肽物质P （SP）的作用下发生分化，SP处理后Nanog和β-catenin的表达趋势相反，这可以被Wnt拮抗剂Dkk-1拮抗。与SP处理组相比，转导后的EpSCs具有更强的增殖能力，并且在SP处理下不发生分化。更重要的是，Nanog过表达后β-catenin表达下调，磷酸化β-catenin表达和磷酸化GSK-3β表达上调。这些结果强烈提示Nanog通过GSK-3β促进β-catenin磷酸化，抑制Wnt/β-catenin信号通路的活性，在维持EpSCs增殖和分化稳态中发挥重要作用。这对于在组织工程应用中精确调控EpSC的增殖和分化具有重要意义。
Skin tissue homeostasis is maintained by a balance between the proliferation and differentiation of epidermal stem cells (EpSCs). EpSC proliferation and differentiation are complex processes regulated by many factors and signaling pathways. This study aimed to explore the connection between the Nanog and the Wnt/β-catenin pathway in the proliferation and differentiation of EpSCs. Our results demonstrated that during the study period, EpSC underwent differentiation when incubated in the presence neuropeptide substance P (SP), there was an opposing expression trend of Nanog and β-catenin after SP treatment, which could be antagonized by the Wnt antagonist, Dkk-1. The transduced EpSCs had a greater proliferative ability than the SP treatment group and they did not undergo differentiation upon SP treatment. More important, β-catenin expression was down-regulated but phosphorylated β-catenin expression and phosphorylated GSK-3β expression was up-regulated upon Nanog overexpression. These results strongly suggest that Nanog plays an important role in maintaining the proliferation and differentiation homeostasis of EpSCs by promoting β-catenin phosphorylation via GSK-3β to inhibit the activity of the Wnt/β-catenin signaling pathway. This is important for precise regulation of proliferation and differentiation of EpSC in the application of tissue engineering.
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DOI：
10.1098/rsif.2012.0525
发表时间：
2013-01-06
期刊：
Journal of the Royal Society, Interface
影响因子：
--
作者：
Luo Y;Lim CL;Nichols J;Martinez-Arias A;Wernisch L
通讯作者：
Wernisch L
影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
2.7
作者：
Gannon HS;Donehower LA;Lyle S;Jones SN
通讯作者：
Jones SN
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1007/978-1-61737-960-4_21
发表时间：
2011-01-01
期刊：
ADIPOSE-DERIVED STEM CELLS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Baer, Patrick C.;Brzoska, Martin;Geiger, Helmut
通讯作者：
Geiger, Helmut