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A Parkinson's disease gene, DJ-1, regulates astrogliosis through STAT3

Authors
Choi, DJ; Kwon, JK; Joe, EH
Citation
Neuroscience letters, 685:144-149, 2018
Journal Title
Neuroscience letters
ISSN
0304-39401872-7972
Abstract
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 3h, 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 muM) and S3I-201 (50 muM), 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.
Keywords
Parkinsons diseaseDJ-1STAT3Astrogliosis
MeSH terms
AnimalsAstrocytes/metabolismGlial Fibrillary Acidic Protein/metabolismGliosis/genetics*Gliosis/metabolismMice, KnockoutParkinson Disease/genetics*Parkinson Disease/metabolismPhosphorylationProtein Deglycase DJ-1/genetics*Protein Deglycase DJ-1/metabolism*STAT3 Transcription Factor/geneticsSTAT3 Transcription Factor/metabolism*Signal Transduction/geneticsSignal Transduction/physiology
DOI
10.1016/j.neulet.2018.08.025
PMID
30171910
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
최, 동주조, 은혜
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