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 |
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Authors: | Wang Chia-Mei Chang Yuan-Yi Sun Synthia H |
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Institution: | Institute of Neuroscience, College of Life Science, National Yang Ming University, Brain Research Center, University System of Taiwan, Taipei, Taiwan, ROC |
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Abstract: | The present study investigates the receptor and mechanisms involved in ATP-stimulated transforming growth factor-beta 1 (TGF-β1) mRNA expression of a type-2 astrocyte cell line, RBA-2. RT-PCR analysis revealed that RBA-2 type-2 astrocytes possess abundant P2X4 and P2X7 receptors. ATP and P2X7 receptor-sensitive agonist, BzATP, both stimulated TGF-β1 mRNA expression in a time and dose-dependent manner. The stimulation required a minimum of 500 μM ATP; BzATP was much more potent that ATP, and P2X7-selective antagonist, oATP, inhibited the effects. In addition, ATP metabolites ADP, AMP and adenosine were ineffective in stimulation of TGF-β1 mRNA expression. Thus, the effect of ATP was mediated through the P2X7 receptors. To investigate further the mechanisms by which the P2X7 receptor mediated the TGF-β1 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-β1 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 P2X7 receptors enhanced TGF-β1 mRNA expression and the effect involved PKC/MAPK signalling pathway in RBA-2 type-2 astrocytes. |
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Keywords: | ATP BzATP ERK1/2 MAPK PKC P2X7 receptor and TGF-β1 |
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