A Parkinson's disease gene, DJ-1, regulates astrogliosis through STAT3. (15th October 2018)

• Record Type: Journal Article
• Authors: Choi, Dong-Joo; Kwon, Jae-Kyung; Joe, Eun-Hye
• Is Part Of: Neuroscience letters. Volume 685(2018)
• Page Start: 144
• Page End: 149
• Publication Date: 2018-10-15
• Subjects: GFAP glial fibrillary acidic protein -- STAT3 signal transducer and activator of transcription 3 -- pSTAT3 phosphorylation of STAT3 -- DPP 5, 15-diphenylporphyrin -- BDNF brain derived neurotrhophic factor -- GDNF glial cell line-derived neurotrophic factor; Parkinsons disease -- DJ-1 -- STAT3 -- Astrogliosis; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.08.025
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: STAT3 phosphorylation is attenuated in DJ-1 KO slices. Inhibition of pSTAT3 attenuates astrogliosis and BDNF/GDNF expression in brain slices. STAT3 and Sox9 independently regulate the astrogliosis. 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 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 μM) and S3I-201 (50 μM), 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.