Y-Box Protein 1 Stimulates Mesangial Cell Proliferation via Activation of ERK1/2
Y-Box Protein 1 Stimulates Mesangial Cell Proliferation via Activation of ERK1/2
复制标题
Y-Box 蛋白 1 通过激活 ERK1/2 刺激系膜细胞增殖
DOI：
10.1159/000228079
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Yang, Tianxin
中科院分区：
文献类型：
--
作者：
Feng, Quancheng;Huang, Songming;Yang, Tianxin
目的：研究Y盒蛋白1（YB - 1）对丝裂原活化蛋白激酶途径的影响，以确定YB - 1诱导的系膜细胞（MC）增殖涉及哪些信号通路。
方法：用pcDNA3.1 - YB - 1转染大鼠系膜细胞系HBZY - 1。通过[H - 3]胸腺嘧啶核苷掺入、细胞计数和细胞周期分析来测定细胞增殖。通过实时逆转录聚合酶链反应和免疫印迹分析检测细胞周期蛋白的表达。通过免疫印迹分析检测c - Raf、MEK1/2和ERK1/2的磷酸化。
结果：转染YB - 1的系膜细胞显示DNA合成增加，细胞周期的S期和G2期细胞数量增多。细胞周期蛋白（细胞周期蛋白A2、细胞周期蛋白D1、细胞周期蛋白E和p27）的表达增加，而p21水平降低。转染YB - 1的系膜细胞中磷酸化的c - Raf激酶、MEK1/2和ERK1/2蛋白的表达水平升高。YB - 1刺激的细胞增殖被ERK1/2的特异性抑制剂U0126阻断。在转化生长因子 - β刺激的系膜细胞中，ERK1/2调节YB - 1的表达，这种作用被U0126抑制。
结论：YB - 1对系膜细胞中的c - Raf、MEK1/2、ERK1/2和细胞周期进程有明显的刺激作用，之后活化的ERK1/2继续上调YB - 1的表达并增强YB - 1的增殖作用。版权所有（C）2009 S. Karger AG，巴塞尔
Aims: To investigate the effects of Y-box protein 1 (YB-1) on the mitogen-activated protein kinase pathway to ascertain which signaling pathway is involved in YB-1-induced mesangial cell (MC) proliferation. Methods: The rat MC line HBZY-1 was transfected with pcDNA3.1-YB-1. Cell proliferation was determined by [H-3] thymidine incorporation, cell counting and cell-cycle analysis. The expression of cyclins was examined by real-time RT-PCR and immunoblotting analysis. Phosphorylation of c-Raf, MEK1/2, and ERK1/2 was detected by immunoblotting analysis. Results: MCs transfected with YB-1 showed an increased DNA synthesis and number of cells in the S and G2 phases of the cell cycle. The expression of cyclins (cyclin A2, cyclin D1, cyclin E and p27) was increased, while p21 levels were decreased. The expression levels of phosphorylated c-Raf kinase, MEK1/2 and the ERK1/2 proteins were elevated in MCs transfected with YB-1. YB-1-stimulated cell proliferation was blocked by U0126, a specific inhibitor of ERK1/2. ERK1/2 regulated YB-1 expression in MCs stimulated with TGF-beta, an effect that was inhibited by U0126. Conclusions: YB-1 has an apparent stimulatory effect on c-Raf, MEK1/2, ERK1/2 and cell-cycle progression in MCs, after which activated ERK1/2 goes on to upregulate YB-1 expression and augment the proliferative effect of YB-1. Copyright (C) 2009 S. Karger AG, Basel