P2X7嘌呤受体激活刺激转化生长因子-β1（TGF-β1）mRNA表达涉及大鼠脑源性2型星形胶质细胞系RBA-2中的蛋白激酶C/丝裂原活化蛋白激酶（PKC/MAPK）信号通路。
Activation of P2X7 purinoceptor-stimulated TGF-beta 1 mRNA expression involves PKC/MAPK signalling pathway in a rat brain-derived type-2 astrocyte cell line, RBA-2.
作者信息
Wang Chia-Mei, Chang Yuan-Yi, Sun Synthia H
机构信息
Institute of Neuroscience, College of Life Science, National Yang Ming University, Brain Research Center, University System of Taiwan, Taipei, Taiwan, ROC.
出版信息
Cell Signal. 2003 Dec;15(12):1129-37. doi: 10.1016/s0898-6568(03)00112-8.
The present study investigates the receptor and mechanisms involved in ATP-stimulated transforming growth factor-beta 1 (TGF-beta 1) mRNA expression of a type-2 astrocyte cell line, RBA-2. RT-PCR analysis revealed that RBA-2 type-2 astrocytes possess abundant P2X(4) and P2X(7) receptors. ATP and P2X(7) receptor-sensitive agonist, BzATP, both stimulated TGF-beta 1 mRNA expression in a time and dose-dependent manner. The stimulation required a minimum of 500 muM ATP; BzATP was much more potent that ATP, and P2X(7)-selective antagonist, oATP, inhibited the effects. In addition, ATP metabolites ADP, AMP and adenosine were ineffective in stimulation of TGF-beta 1 mRNA expression. Thus, the effect of ATP was mediated through the P2X(7) receptors. To investigate further the mechanisms by which the P2X(7) receptor mediated the TGF-beta 1 mRNA expression, the cells were treated with inhibitors for mitogen-activated kinase (MAPK) or protein kinase C (PKC), PD98059 or GF109203X, respectively. Both PD98059 and GF109203X inhibited the ATP-stimulated TGF-beta 1 mRNA expression. Furthermore, ATP and BzATP stimulated ERK1/2 activation and the activation was inhibited by PKC inhibitors, GF109203X and Gö6976. In conclusion, activation of P2X(7) receptors enhanced TGF-beta 1 mRNA expression and the effect involved PKC/MAPK signalling pathway in RBA-2 type-2 astrocytes.
本研究调查了参与ATP刺激的2型星形胶质细胞系RBA - 2中转化生长因子β1（TGF - β1）mRNA表达的受体和机制。逆转录聚合酶链反应（RT - PCR）分析显示，RBA - 2型星形胶质细胞拥有丰富的P2X(4)和P2X(7)受体。ATP和P2X(7)受体敏感激动剂BzATP均以时间和剂量依赖性方式刺激TGF - β1 mRNA表达。该刺激至少需要500μM ATP；BzATP比ATP更有效，且P2X(7)选择性拮抗剂oATP可抑制其作用。此外，ATP代谢产物ADP、AMP和腺苷对TGF - β1 mRNA表达的刺激无效。因此，ATP的作用是通过P2X(7)受体介导的。为了进一步研究P2X(7)受体介导TGF - β1 mRNA表达的机制，分别用丝裂原活化激酶（MAPK）或蛋白激酶C（PKC）抑制剂PD98059或GF109203X处理细胞。PD98059和GF109203X均抑制了ATP刺激的TGF - β1 mRNA表达。此外，ATP和BzATP刺激细胞外信号调节激酶1/2（ERK1/2）活化，且该活化被PKC抑制剂GF109203X和Gö6976抑制。总之，P2X(7)受体的激活增强了TGF - β1 mRNA表达，且该作用涉及RBA - 2型星形胶质细胞中的PKC/MAPK信号通路。
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