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

Environ Toxicol. 2021 Nov;36(11):2302-2312. doi: 10.1002/tox.23344. Epub 2021 Aug 29.

Abstract

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.

Keywords: FGF2; Parkinson's disease; apoptosis; autophagy; miR-497-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Fibroblast Growth Factor 2 / genetics
  • Mice
  • MicroRNAs / genetics*
  • Parkinson Disease* / genetics
  • Up-Regulation

Substances

  • MicroRNAs
  • mirn497 microRNA, mouse
  • Fibroblast Growth Factor 2