MicroRNA‑195 triggers neuroinflammation in Parkinson's disease in a Rho‑associated kinase 1‑dependent manner

Ren,Yi; Li,Huajie; Xie,Wei; Wei,Ning; Liu,Meng

doi:10.3892/mmr.2019.10176

MicroRNA‑195 triggers neuroinflammation in Parkinson's disease in a Rho‑associated kinase 1‑dependent manner

Authors:
- Yi Ren
- Huajie Li
- Wei Xie
- Ning Wei
- Meng Liu
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Affiliations: Department of Neurology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China
Published online on: April 19, 2019 https://doi.org/10.3892/mmr.2019.10176
Pages: 5153-5161

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Abstract

Parkinson's disease (PD) is a common progressive neurodegenerative disorder occurring in older individuals. Mechanistically, neuroinflammation is a central pathological change in the progression of PD. Activation of microglia is widely considered to be a major trigger for neuroinflammation. Certain microRNAs (miRs) are key factors in inhibiting or stimulating inflammation during the occurrence and development of PD, among which miR‑195 may be a potential crucial biomarker. However, the underlying pathological mechanisms remain unclear. To investigate the pathogenesis of PD, lipopolysaccharide (LPS) was used to establish an in vitro model of microglia activation in the present study. It was revealed that miR‑195 expression was decreased in LPS‑stimulated BV2 cells, suggesting a potential mechanism of action of miR‑195 on microglia activation. Furthermore, gain‑ and loss‑of‑function experiments were performed by successful transfection of microglia with miR‑195 mimics or inhibitors. The results demonstrated that miR‑195 overexpression inhibited the release of pro‑inflammatory cytokines, including inducible nitric oxide synthase, interleukin‑6 (IL‑6) and tumor necrosis factor‑α, but induced the release of anti‑inflammatory cytokines in LPS‑treated BV2 cells, including IL‑4 and IL‑10. In addition, Rho‑associated kinase 1 (ROCK1), which is negatively regulated by miR‑195, was increased in LPS‑stimulated BV2 cells. ROCK1 knockdown with small interfering RNA exhibited the same effect as miR‑195 overexpression on regulating microglia status, suggesting that the miR‑195/ROCK1 interaction serves a central role in inducing microglia activation. Furthermore, inhibition of ROCK1 impaired cell viability and proliferation but induced cell apoptosis in LPS‑treated miR‑195‑deficient BV2 cells. The present results suggest that miR‑195 is a potential therapeutic target for PD.

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