机构：[1]Institute of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China四川省人民医院[2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China四川省人民医院
Aims The neurotropic growth factor PDGF-BB was shown to have vital neurorestorative functions in various animal models of Parkinson's disease (PD). Previous studies indicated that the regenerative property of PDGF-BB contributes to the increased intensity of tyrosine hydroxylase (TH) fibers in vivo. However, whether PDGF-BB directly modulates the expression of TH, and the underlying mechanism is still unknown. We will carefully examine this in our current study. Method MPTP-lesion mice received PDGF-BB treatment via intracerebroventricular (i.c.v) administration, and the expression of TH in different brain regions was assessed by RT-PCR, Western blot, and immunohistochemistry staining. The molecular mechanisms of PDGF-BB-mediated TH upregulation were examined by RT-PCR, Western blot, ChIP assay, luciferase reporter assay, and immunocytochemistry. Results We validated a reversal expression of TH in MPTP-lesion mice upon i.c.v administration of PDGF-BB for seven days. Similar effects of PDGF-BB-mediated TH upregulation were also observed in MPP+-treated primary neuronal culture and dopaminergic neuronal cell line SH-SY5Y cells. We next demonstrated that PDGF-BB rapidly activated the pro-survival PI3K/Akt and MAPK/ERK signaling pathways, as well as the downstream CREB in SH-SY5Y cells. We further confirmed the significant induction of p-CREB in PDGF-BB-treated animals in vivo. Using a genetic approach, we demonstrated that the transcription factor CREB is critical for PDGF-BB-mediated TH expression. The activation and nucleus translocation of CREB were promoted in PDGF-BB-treated SH-SY5Y cells, and the enrichment of CREB on the promoter region of TH gene was also increased upon PDGF-BB treatment. Conclusion Our data demonstrated that PDGF-BB directly regulated the expression of TH via activating the downstream Akt/ERK/CREB signaling pathways. Our finding will further support the therapeutic potential of PDGF-BB in PD, and provide the possibility that targeting PDGF signaling can be harnessed as an adjunctive therapy in PD in the future.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81601125, 31601137, 81673338]; Central University Basic Scientific Research Business Expenses Special [A03019023801206, ZYGX2017KYQD169]
第一作者机构：[1]Institute of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China[2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China[2]School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China[*1]Institute of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
推荐引用方式(GB/T 7714)：
Chen Huan,Teng Yan,Chen Xingmin,et al.Platelet-derived growth factor (PDGF)-BB protects dopaminergic neurons via activation of Akt/ERK/CREB pathways to upregulate tyrosine hydroxylase[J].CNS NEUROSCIENCE & THERAPEUTICS.2021,27(11):1300-1312.doi:10.1111/cns.13708.
APA：
Chen, Huan,Teng, Yan,Chen, Xingmin,Liu, Zhihao,Geng, Fan...&Yang, Lu.(2021).Platelet-derived growth factor (PDGF)-BB protects dopaminergic neurons via activation of Akt/ERK/CREB pathways to upregulate tyrosine hydroxylase.CNS NEUROSCIENCE & THERAPEUTICS,27,(11)
MLA：
Chen, Huan,et al."Platelet-derived growth factor (PDGF)-BB protects dopaminergic neurons via activation of Akt/ERK/CREB pathways to upregulate tyrosine hydroxylase".CNS NEUROSCIENCE & THERAPEUTICS 27..11(2021):1300-1312
