Silencing of miR-497-5p inhibits cell apoptosis and promotes autophagy in Parkinson's disease by upregulation of FGF2

被引:30
|
作者
Zhu, Wenjie [1 ]
Zhang, Hui [2 ]
Gao, Jun [3 ]
Xu, Yun [4 ]
机构
[1] Nanjing Med Univ, Sir Run Run Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Sir Run Run Hosp, Dept Cardiol, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Sch Basic Med Sci, Dept Neurobiol, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Univ, Dept Neurol, Med Sch, Affiliated Drum Tower Hosp, Nanjing, Jiangsu, Peoples R China
关键词
apoptosis; autophagy; FGF2; miR-497-5p; Parkinson's disease; UBIQUITINATED PROTEIN ACCUMULATION; MYOCARDIAL ISCHEMIA/REPERFUSION; MODEL; RECOVERY; PATHWAY; MIRNAS;
D O I
10.1002/tox.23344
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Parkinson's disease (PD) is a progressive neurodegenerative disorder with increasing prevalence in elderly individuals globally. MicroRNAs (miRNAs) have been confirmed to participate in the pathogenesis of various neurodegenerative diseases, including PD. MiR-497-5p is previously reported to be upregulated in PD. The present study was designed to further explore the function of miR-497-5p in PD. MiR-497-5p was significantly upregulated in 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells. Inhibition of miR-497-5p suppressed the cell apoptosis and triggered autophagy of MPP+-treated SH-SY5Y cells. Further, miR-497-5p targeted fibroblast growth factor-2 (FGF2) in MPP+-treated SH-SY5Y cells. Subsequently, rescue assays revealed that miR-497-5p regulated apoptosis and autophagy of MPP+-treated SH-SY5Y cells by mediation on FGF2. In addition, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mice models were established. The results exhibited that silencing of miR-497-5p improved mice bradykinesia, reduced cell apoptosis and induced autophagy in PD mice by FGF2. In conclusion, silencing of miR-497-5p alleviates PD by suppressing cell apoptosis and promoting autophagy in a FGF2 dependent manner, which will provide a novel target for Parkinson's disease management.
引用
收藏
页码:2302 / 2312
页数:11
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