A Parkinson's disease gene, DJ-1, regulates astrogliosis through STAT3
A Parkinson's disease gene, DJ-1, regulates astrogliosis through STAT3
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DOI：
10.1016/j.neulet.2018.08.025
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发表时间：
2018-10-15
影响因子：
2.5
通讯作者：
Joe, Eun-Hye
中科院分区：
文献类型：
--
作者：
Choi, Dong-Joo;Kwon, Jae-Kyung;Joe, Eun-Hye
在受损的大脑中，星形胶质细胞被激活并增加GFAP表达;这种现象称为星形胶质细胞增生。以前，我们已经报道了DJ-1，帕金森病基因，积极调节受损大脑中的星形胶质细胞增生。此外，已知STAT 3在星形胶质细胞增生的调节中发挥关键作用。本研究的目的是评估DJ-1是否通过STAT 3激活调节星形胶质细胞增生。这项研究的结果表明，DJ-1是STAT 3激活的正调节因子，STAT 3是星形胶质细胞增生最重要的介质。在从野生型（WT）小鼠获得的脑切片培养物中，STAT 3在3小时内被激活，这通过其磷酸化为pSTAT 3来证明，并且GFAP表达在切片制备后2天内增加。有趣的是，DJ-1基因敲除脑片中pSTAT 3和GFAP的水平与WT相比有所减弱。STAT 3抑制剂DPP（5 μ M）和S3 I-201（50 μ M）减少BDNF、GDNF和GFAP的表达。然而，STAT 3抑制剂不影响Sox 9的mRNA水平，Sox 9是星形胶质细胞增生的另一个重要调节因子。此外，Sox 9 siRNA不影响STAT 3磷酸化。这些结果表明STAT 3和Sox 9可能是DJ-1的独立靶点。
In the injured brain, astrocytes become activated and increase GFAP expression; a phenomenon termed as astrogliosis. Previously, we have reported that DJ-1, a Parkinson's disease gene, positively regulates astrogliosis in the injured brain. Moreover, STAT3 is known to play a key role in the regulation of astrogliosis. The purpose of this study was to evaluate whether DJ-1 regulates astrogliosis, via STAT3 activation. The results of this study reveal that DJ-1 is a positive regulator of STAT3 activation, the most important mediator of astrogliosis. In brain slice cultures obtained from wild-type (WT) mice, STAT3 was activated, as demonstrated by its phosphorylation to pSTAT3, within 3 h, and GFAP expression was increased within 2 days after slice preparation. Interestingly, levels of pSTAT3 and GFAP in DJ-1 knockout brain slice were attenuated compared with that of WT. STAT3 inhibitors, DPP (5 mu M) and S3I-201 (50 mu M), reduced expression of BDNF, GDNF, and GFAP. However, the STAT3 inhibitors did not affect mRNA levels of Sox9, another important regulator of astrogliosis. Additionally, Sox9 siRNAs did not affect STAT3 phosphorylation. These results indicate that STAT3 and Sox9 may be the independent targets of DJ-1.