全反式维甲酸诱导 P19 细胞分化为参与 PI3K/Akt/GSK3β 信号通路的神经元。,Journal of Cellular Biochemistry

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全反式维甲酸诱导 P19 细胞分化为参与 PI3K/Akt/GSK3β 信号通路的神经元。
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2020-01-21 , DOI: 10.1002/jcb.29659
Fang Fu ₁ , Lu-Shan Li ₁ , Ru Li ₁ , Qiong Deng ₁ , Qiu-Xia Yu ₁ , Xin Yang ₁ , Min Pan ₁ , Jin Han ₁ , Li Zhen ₁ , Li-Na Zhang ₁ , Ting-Ying Lei ₁ , Dong-Zhi Li ₁ , Can Liao ₁

Affiliation

多能小鼠胚胎癌细胞系 P19 被广泛用作研究全反式维甲酸 (RA) 诱导的神经元分化的模型；然而，参与这一过程的信号通路仍不清楚。本研究旨在揭示 RA 诱导 P19 细胞神经元分化的分子机制。实时定量聚合酶链反应和蛋白质印迹分析用于确定神经元特异性标志物的表达，而流式细胞术用于分析细胞周期和细胞凋亡。使用高通量测序分析 RA 诱导的 P19 细胞神经元分化中信使 RNA (mRNA) 的表达谱，并通过生物信息学分析确定差异表达 mRNA (DEM) 的功能。RA 诱导 III 类 β-微管蛋白 (TUBB3) 和神经丝培养基 (NEFM) mRNA 表达增加，表明 RA 成功诱导 P19 细胞的神经元分化。细胞凋亡不受影响；然而，细胞增殖减少。我们发现了 4117 个 DEM，它们富含磷酸肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）信号通路、Wnt 信号通路和细胞周期。特别是，可以在 PI3K/Akt 信号通路网络中识别出一些 DEM，如 PI3K、Akt、糖原合酶激酶 3β (GSK3β)、细胞周期蛋白依赖性激酶 4 (CDK4)、P21 和 Bax。RA 显着增加 PI3K、Akt、磷酸化 Akt、GSK3β、磷酸化 GSK3β、CDK4 和 P21 的蛋白表达，但降低了 Bax 蛋白的表达。Akt 抑制剂影响 RA 诱导的 P19 细胞中 TUBB3 和 NEFM mRNA 表达的增加。RA 诱导 P19 细胞神经元分化的分子机制可能与 PI3K/Akt/GSK3β 信号通路有关。神经元分化的P19细胞增殖能力下降可能与细胞周期蛋白的表达有关。

"点击查看英文标题和摘要"

All-trans-retinoid acid induces the differentiation of P19 cells into neurons involved in the PI3K/Akt/GSK3β signaling pathway.

The pluripotent mouse embryonal carcinoma cell line P19 is widely used as a model for research on all‐trans‐retinoid acid (RA)‐induced neuronal differentiation; however, the signaling pathways involved in this process remain unclear. This study aimed to reveal the molecular mechanism underlying the RA‐induced neuronal differentiation of P19 cells. Real‐time quantitative polymerase chain reaction and Western blot analysis were used to determine the expression of neuronal‐specific markers, whereas flow cytometry was used to analyze cell cycle and cell apoptosis. The expression profiles of messenger RNAs (mRNAs) in RA‐induced neuronal differentiation of P19 cells were analyzed using high‐throughput sequencing, and the functions of differentially expressed mRNAs (DEMs) were determined by bioinformatics analysis. RA induced an increase in both class III β‐tubulin (TUBB3) and neurofilament medium (NEFM) mRNA expression, indicating that RA successfully induces neuronal differentiation of P19 cells. Cell apoptosis was not affected; however, cell proliferation decreased. We found 4117 DEMs, which were enriched in the phosphoinositide 3‐kinase/protein kinase B (PI3K/Akt) signaling pathway, Wnt signaling pathway, and cell cycle. Particularly, a few DEMs could be identified in the PI3K/Akt signaling pathway networks, such as PI3K, Akt, glycogen synthase kinase‐3β (GSK3β), cyclin‐dependent kinase 4 (CDK4), P21, and Bax. RA significantly increased the protein expression of PI3K, Akt, phosphorylated Akt, GSK3β, phosphorylated GSK3β, CDK4, and P21, but it reduced Bax protein expression. The Akt inhibitor affected the increase of TUBB3 and NEFM mRNA expression in RA‐induced P19 cells. The molecular mechanism underlying the RA‐induced neuronal differentiation of P19 cells is potentially involved in the PI3K/Akt/GSK3β signaling pathway. The decreased cell proliferation ability of neuronally differentiated P19 cells could be associated with the expression of cell cycle proteins.

更新日期：2020-01-21

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