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
  • View Affiliations

  • Published online on: April 19, 2019     https://doi.org/10.3892/mmr.2019.10176
  • Pages: 5153-5161
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.

References

1 

Zafar S and Yaddanapudi SS: Parkinson disease. StatPearls (Internet). Treasure Island (FL): StatPearls Publishing; 2018

2 

Joshi N and Singh S: Updates on immunity and inflammation in Parkinson disease pathology. J Neurosci Res. 96:379–390. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Sunkaria A, Wani WY, Sharma DR and Gill KD: Dichlorvos exposure results in activation induced apoptotic cell death in primary rat microglia. Chem Res Toxicol. 25:1762–1770. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Oh SE, Park HJ, He L, Skibiel C, Junn E and Mouradian MM: The Parkinson's disease gene product DJ-1 modulates miR-221 to promote neuronal survival against oxidative stress. Redox Biol. 19:62–73. 2018. View Article : Google Scholar : PubMed/NCBI

5 

Lee J, Park EJ and Kiyono H: MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation. BMB Rep. 49:263–269. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Arshad AR, Sulaiman SA, Saperi AA, Jamal R, Mohamed Ibrahim N and Abdul Murad NA: MicroRNAs and target genes as biomarkers for the diagnosis of early onset of parkinson disease. Front Mol Neurosci. 10:3522017. View Article : Google Scholar : PubMed/NCBI

7 

Cao XY, Lu JM, Zhao ZQ, Li MC, Lu T, An XS and Xue LJ: MicroRNA biomarkers of Parkinson's disease in serum exosome-like microvesicles. Neurosci Lett. 644:94–99. 2017. View Article : Google Scholar : PubMed/NCBI

8 

Ding H, Huang Z, Chen M, Wang C, Chen X, Chen J and Zhang J: Identification of a panel of five serum miRNAs as a biomarker for Parkinson's disease. Parkinsonism Relat Disord. 22:68–73. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Ma X, Yao H, Yang Y, Jin L, Wang Y, Wu L, Yang S and Cheng K: miR-195 suppresses abdominal aortic aneurysm through the TNF-alpha/NF-kappaB and VEGF/PI3K/Akt pathway. Int J Mol Med. 41:2350–2358. 2018.PubMed/NCBI

10 

Bras JP, Silva AM, Calin GA, Barbosa MA, Santos SG and Almeida MI: miR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells. PloS One. 12:e01885302017. View Article : Google Scholar : PubMed/NCBI

11 

Han C and Wang W: MicroRNA-129-5p suppresses cell proliferation, migration and invasion via targeting ROCK1 in osteosarcoma. Mol Med Rep. 17:4777–4784. 2018.PubMed/NCBI

12 

Moon HG, Cao Y, Yang J, Lee JH, Choi HS and Jin Y: Lung epithelial cell-derived extracellular vesicles activate macrophage-mediated inflammatory responses via ROCK1 pathway. Cell Death Dis. 6:e20162015. View Article : Google Scholar : PubMed/NCBI

13 

Liang H, Liao M, Zhao W, Zheng X, Xu F, Wang H and Huang J: CXCL16/ROCK1 signaling pathway exacerbates acute kidney injury induced by ischemia-reperfusion. Biomed Pharmacother. 98:347–356. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Liu Y, Liu J, Wang L, Yang X and Liu X: MicroRNA195 inhibits cell proliferation, migration and invasion in laryngeal squamous cell carcinoma by targeting ROCK1. Mol Med Rep. 16:7154–7162. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Jin H, Lian N, Zhang F, Chen L, Chen Q, Lu C, Bian M, Shao J, Wu L and Zheng S: Activation of PPARgamma/P53 signaling is required for curcumin to induce hepatic stellate cell senescence. Cell death Dis. 7:e21892016. View Article : Google Scholar : PubMed/NCBI

16 

Gomez-Nicola D and Perry VH: Microglial dynamics and role in the healthy and diseased brain: A paradigm of functional plasticity. Neuroscientist. 21:169–184. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Ma X, Zou L, Li X, Chen Z, Lin Q and Wu X: MicroRNA-195 regulates docetaxel resistance by targeting clusterin in prostate cancer. Biomed Pharmacother. 99:445–450. 2018. View Article : Google Scholar : PubMed/NCBI

18 

Song LY, Ma YT, Wu CF, Wang CJ, Fang WJ and Liu SK: MicroRNA-195 activates hepatic stellate cells in vitro by targeting Smad7. BioMed Res Int. 2017:19456312017. View Article : Google Scholar : PubMed/NCBI

19 

Zhou B, Sun C, Hu X, Zhan H, Zou H, Feng Y, Qiu F, Zhang S, Wu L and Zhang B: MicroRNA-195 suppresses the progression of pancreatic cancer by targeting DCLK1. Cell Physiol Biochem. 44:1867–1881. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Tiwari A, Singh P, Jaitley P, Sharma S, Prakash A, Mandil R, Choudhury S, Gangwar NK and Garg SK: Eucalyptus robusta leaves methanolic extract suppresses inflammatory mediators by specifically targeting TLR4/TLR9, MPO, COX2, iNOS and inflammatory cytokines in experimentally-induced endometritis in rats. J Ethnopharmacol. 213:149–158. 2018. View Article : Google Scholar : PubMed/NCBI

21 

Mavrogonatou E, Konstantinou A and Kletsas D: Long-term exposure to TNF-alpha leads human skin fibroblasts to a p38 MAPK- and ROS-mediated premature senescence. Biogerontology. 19:237–249. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Gonsalves C and Kalra VK: Endothelin-1-induced macrophage inflammatory protein-1beta expression in monocytic cells involves hypoxia-inducible factor-1alpha and AP-1 and is negatively regulated by microRNA-195. J Immunol. 185:6253–6264. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Ding J, Huang S, Wang Y, Tian Q, Zha R, Shi H, Wang Q, Ge C, Chen T, Zhao Y, et al: Genome-wide screening reveals that miR-195 targets the TNF-alpha/NF-kappaB pathway by down-regulating IkappaB kinase alpha and TAB3 in hepatocellular carcinoma. Hepatology. 58:654–666. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Wang Y, Lu Y, Chai J, Sun M, Hu X, He W, Ge M and Xie C: Y-27632, a Rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus. Biomed Pharmacotherapie. 88:359–366. 2017. View Article : Google Scholar

25 

Askew K, Li K, Olmos-Alonso A, Garcia-Moreno F, Liang Y, Richardson P, Tipton T, Chapman MA, Riecken K, Beccari S, et al: Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Rep. 18:391–405. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

June 2019
Volume 19 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Ren, Y., Li, H., Xie, W., Wei, N., & Liu, M. (2019). MicroRNA‑195 triggers neuroinflammation in Parkinson's disease in a Rho‑associated kinase 1‑dependent manner. Molecular Medicine Reports, 19, 5153-5161. https://doi.org/10.3892/mmr.2019.10176
MLA
Ren, Y., Li, H., Xie, W., Wei, N., Liu, M."MicroRNA‑195 triggers neuroinflammation in Parkinson's disease in a Rho‑associated kinase 1‑dependent manner". Molecular Medicine Reports 19.6 (2019): 5153-5161.
Chicago
Ren, Y., Li, H., Xie, W., Wei, N., Liu, M."MicroRNA‑195 triggers neuroinflammation in Parkinson's disease in a Rho‑associated kinase 1‑dependent manner". Molecular Medicine Reports 19, no. 6 (2019): 5153-5161. https://doi.org/10.3892/mmr.2019.10176