Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways
Synergistic activity of activin A and basic fibroblast growth factor on tyrosine hydroxylase expression through Smad3 and ERK1/ERK2 MAPK signaling pathways
复制标题
DOI：
10.1677/joe.1.05978
复制
发表时间：
2005-03-01
影响因子：
4
通讯作者：
Sugino, H
中科院分区：
文献类型：
--
作者：
Bao, YL;Tsuchida, K;Sugino, H
激活素此前已被证明是一种神经细胞生存因子，并对神经元具有神经营养作用。然而，激活素在调节中枢神经系统神经递质表达中的作用以及参与这一过程的确切机制还知之甚少。在本研究中，我们报道了激活素A和碱性成纤维细胞生长因子协同增加了小鼠E14纹状体原代细胞和海马神经细胞系HT22酪氨酸羟化酶(TH)的蛋白水平，并显著增加了TH的mRNA水平。激活素A和碱性成纤维细胞生长因子协同刺激Smad3核转位，并特异性激活ERK1/2，但不能激活p38或JNK。有趣的是，MEK的特异性抑制剂U0126有效地阻断了激活素A和碱性成纤维细胞生长因子对TH启动子活性的诱导，表明激活素A与碱性成纤维细胞生长因子信号合作，通过选择性激活ERK型MAPK在小鼠纹状体和HT22细胞中诱导TH基因的表达。这些数据提示激活素A可能与碱性成纤维细胞生长因子共同作用于TH阳性神经元的发育。
Activin has previously been shown to act as a nerve cell survival factor and to have neurotrophic effects on neurons. However, the role of activin in regulating neurotransmitter expression in the central nervous system and the exact mechanisms involved in this process are poorly understood. In the present study, we report that activin A and basic fibroblast growth factor (bFGF) synergistically increased the protein level of tyrosine hydroxylase (TH), and also greatly increased the TH mRNA level, in both mouse E14 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and bFGF cooperatively stimulated nuclear translocation of Smad3 and specifically activated ERK1/2, but not p38 or JNK. Interestingly, a specific inhibitor for MEK, U0126, efficiently blocked the induction of TH promoter activity by activin A and bFGF, indicating that activin A collaborated with bFGF signaling to induce the TH gene through selective activation of ERK-type MAP kinase in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with bFGF for the development of TH-positive neurons.