BMP enhances transcriptional responses to NGF during PC12 cell differentiation
BMP enhances transcriptional responses to NGF during PC12 cell differentiation
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DOI：
10.1007/s11064-005-6868-6
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Ebendal, T
中科院分区：
文献类型：
--
作者：
Lönn, P;Zaia, K;Ebendal, T
骨形态发生蛋白（BMPs）促进神经生长因子（NGF）刺激的PC12细胞的神经突生长。为了研究这种增强作用的机制，采用实时荧光定量PCR技术分析了45个基因的表达情况。单独用NGF处理1小时后，已观察到Egr1-4、Hes1、Junb、Jun和Fos等10个即时早期基因的表达显著增加。NGF + BMP4在1 h时进一步增加了这些转录本，并激活了18个额外的基因。BMP4单独诱导Smad6、Mtap1b和Hes1。Egr3是受NGF和BMP4上调最强烈的基因。然而，荧光素酶分析显示克隆的Egr3近端启动子不参与BMP4增强。通过显性阴性构建体阻断Egr3和Junb功能可减少刺激条件下的神经突生长，证明Egr和Jun家族成员的激活对于PC12细胞对NGF和BMP4的最大反应是必要的。
Bone morphogenetic proteins (BMPs) enhance neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells. To investigate the mechanism of this potentiating effect, real-time PCR was used to analyze the expression of 45 selected genes. A robust increase in expression of 10 immediate early genes including Egr1-4, Hes1, Junb, Jun and Fos was observed already after 1 h treatment with NGF alone. NGF plus BMP4 further increased these transcripts at 1 h and activated 18 additional genes. BMP4 alone induced Smad6, Mtap1b and Hes1. Egr3 was the gene most strongly upregulated by NGF and BMP4. However, luciferase assays showed that the cloned Egr3 proximal promoter was not involved in the BMP4 potentiation. Blocking Egr3 and Junb function by dominant-negative constructs reduced neurite outgrowth under stimulating conditions, proving that activation of members of both the Egr and Jun families is necessary for maximal PC12 cell response to NGF and BMP4.