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miR-497-5p 的沉默通过上调 FGF2 抑制帕金森病中的细胞凋亡并促进自噬。

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

机构信息

Department of Neurology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Cardiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

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.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,在全球老年人群中的发病率不断上升。microRNAs(miRNAs)已被证实参与了多种神经退行性疾病的发病机制,包括 PD。先前有报道称 miR-497-5p 在 PD 中上调。本研究旨在进一步探讨 miR-497-5p 在 PD 中的作用。miR-497-5p 在 1-甲基-4-苯基吡啶(MPP)处理的 SH-SY5Y 细胞中显著上调。抑制 miR-497-5p 可抑制 MPP 处理的 SH-SY5Y 细胞的细胞凋亡并触发自噬。此外,miR-497-5p 在 MPP 处理的 SH-SY5Y 细胞中靶向成纤维细胞生长因子-2(FGF2)。随后,挽救实验表明,miR-497-5p 通过介导 FGF2 调节 MPP 处理的 SH-SY5Y 细胞的凋亡和自噬。此外,建立了 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠模型。结果表明,miR-497-5p 的沉默通过 FGF2 改善了 PD 小鼠的运动迟缓,减少了细胞凋亡并诱导了 PD 小鼠的自噬。总之,通过依赖于 FGF2 的方式抑制细胞凋亡和促进自噬,沉默 miR-497-5p 可减轻 PD,为帕金森病的管理提供了新的靶点。

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