miR‑183 inhibits microglia activation and expression of inflammatory factors in rats with cerebral ischemia reperfusion via NF‑κB signaling pathway

Xiang,Bo; Zhong,Ping; Fang,Lei; Wu,Xianxian; Song,Yuqiang; Yuan,Haicheng

doi:10.3892/etm.2019.7827

miR‑183 inhibits microglia activation and expression of inflammatory factors in rats with cerebral ischemia reperfusion via NF‑κB signaling pathway

Authors:
- Bo Xiang
- Ping Zhong
- Lei Fang
- Xianxian Wu
- Yuqiang Song
- Haicheng Yuan
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Affiliations: The Second Department of Neurology, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China, Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: July 30, 2019 https://doi.org/10.3892/etm.2019.7827
Pages: 2540-2546
Copyright: © Xiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ischemic stroke represents 87% of all strokes, and is the third leading cause of disability and mortality worldwide. The cause of ischemic stroke is the obstruction of blood flow through the artery that supplies oxygen‑rich blood to the brain, with ischemia‑reperfusion injury as its major cause. microRNAs (miRNA) are small non‑coding RNAs, which serve important roles in the regulation of gene expression at the post‑transcription level. The aim of the present study was to investigate the effect of miRNA‑183 (miR‑183) on microglia activation in rats with cerebral ischemia‑reperfusion injury. To this end, a rat cerebral ischemia‑reperfusion injury model was established. The results indicated that miR‑183 expression was decreased by cerebral ischemia‑reperfusion. In addition, treatment using miR‑183 agomir significantly reduced the neurological function scores, percentage of cerebral infarction volume, and ionized calcium‑binding adapter molecule‑1 (IBA‑1)‑positive cells in the CA1 area of the hippocampus in rats subjected to cerebral ischemia‑reperfusion injury, implicating a neuroprotective role for miR‑183. MiR‑183 agomir treatment also decreased the expression of pro‑inflammatory‑associated proteins interleukin (IL)‑1β, IL‑6 and tumor necrosis factor (TNF)‑α. Finally, the expression of the nuclear factor (NF)‑κB p65 and IκBα was decreased and increased by miR‑183 agomir treatment, respectively, indicating inhibition of the NF‑κB signaling pathway. These observations suggest that miR‑183 regulates the activation of microglia in rats with cerebral ischemia‑reperfusion injury by inhibiting the NF‑κB signaling pathway.

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1	Mendis S, Davis S and Norrving B: Organizational update: The world health organization global status report on noncommunicable diseases 2014; One more landmark step in the combat against stroke and vascular disease. Stroke. 46:e121–122. 2015. View Article : Google Scholar : PubMed/NCBI
2	Zhang R, Zhang Z and Chopp M: Function of neural stem cells in ischemic brain repair processes. J Cereb Blood Flow Metab. 36:2034–2043. 2016. View Article : Google Scholar : PubMed/NCBI
3	Schaller B and Graf R: Cerebral ischemia and reperfusion: The pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab. 24:351–371. 2004. View Article : Google Scholar : PubMed/NCBI
4	Baird AE, Donnan GA, Austin MC, Fitt GJ, Davis SM and McKay WJ: Reperfusion after thrombolytic therapy in ischemic stroke measured by single-photon emission computed-tomography. Stroke. 25:79–85. 1994. View Article : Google Scholar : PubMed/NCBI
5	Lee JM, Grabb MC, Zipfel GJ and Choi DW: Brain tissue responses to ischemia. J Clin Invest. 106:723–731. 2000. View Article : Google Scholar : PubMed/NCBI
6	Blakeley JO and Llinas RH: Thrombolytic therapy for acute ischemic stroke. J Neurol Sci. 261:55–62. 2007. View Article : Google Scholar : PubMed/NCBI
7	Khoshnam SE, Winlow W, Farzaneh M, Farbood Y and Moghaddam HF: Pathogenic mechanisms following ischemic stroke. Neurol Sci. 38:1167–1186. 2017. View Article : Google Scholar : PubMed/NCBI
8	Zhang CX: MicroRNomics: A newly emerging approach for disease biology. Physiol Genomics. 33:139–147. 2008. View Article : Google Scholar : PubMed/NCBI
9	Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI
10	Griffiths-Jones S, Saini HK, van Dongen S and Enright AJ: miRBase: Tools for microRNA genomics. Nucleic Acids Res 36 (Database Issue). D154–D158. 2008.
11	Kloosterman WP and Plasterk RH: The diverse functions of MicroRNAs in animal development and disease. Dev Cell. 11:441–450. 2006. View Article : Google Scholar : PubMed/NCBI
12	Felekkis K, Touvana E, Stefanou CH and Deltas C: microRNAs: A newly described class of encoded molecules that play a role in health and disease. Hippokratia. 14:236–240. 2010.PubMed/NCBI
13	Ouyang YB, Stary CM, Yang GY and Giffard R: microRNAs: Innovative targets for cerebral ischemia and stroke. Curr Drug Targets. 14:90–101. 2013. View Article : Google Scholar : PubMed/NCBI
14	Saugstad JA: MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotection, and neurodegeneration. J Cereb Blood Flow Metab. 30:1564–1576. 2010. View Article : Google Scholar : PubMed/NCBI
15	Li GW, Morris-Blanco KC, Lopez MS, Yang T, Zhao H, Vemuganti R and Luo Y: Impact of microRNAs on ischemic stroke: From pre- to post-disease. Prog Neurobiol. 163-164:59–78. 2018. View Article : Google Scholar : PubMed/NCBI
16	Jeyaseelan K, Lim KY and Armugam A: MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke. 39:959–966. 2008. View Article : Google Scholar : PubMed/NCBI
17	Dharap A, Bowen K, Place R, Li LC and Vemuganti R: Transient focal ischemia induces extensive temporal changes in rat cerebral MicroRNAome. J Cereb Blood Flow Metab. 29:675–687. 2009. View Article : Google Scholar : PubMed/NCBI
18	Sørensen SS, Nygaard AB, Nielsen MY, Jensen K and Christensen T: miRNA expression profiles in cerebrospinal fluid and blood of patients with acute ischemic stroke. Transl Stroke Res. 5:711–718. 2014. View Article : Google Scholar : PubMed/NCBI
19	Li SH, Su SY and Liu JL: Differential regulation of microRNAs in patients with ischemic stroke. Curr Neurovasc Res. 12:214–221. 2015. View Article : Google Scholar : PubMed/NCBI
20	Saugstad JA: Non-coding RNAs in stroke and neuroprotection. Front Neurol. 6:502015. View Article : Google Scholar : PubMed/NCBI
21	Liu da Z, Jickling GC, Ander BP, Hull H, Zhan X, Cox C, Shroff N, Dykstra-Aiello C, Stamova B and Sharp FR: Elevating microRNA-122 in blood improves outcomes after temporary middle cerebral artery occlusion in rats. J Cereb Blood Flow Metab. 36:1374–1383. 2016. View Article : Google Scholar : PubMed/NCBI
22	Khoshnam SE, Winlow W and Farzaneh M: The Interplay of MicroRNAs in the inflammatory mechanisms following ischemic stroke. J Neuropathol Exp Neurol. 76:548–561. 2017. View Article : Google Scholar : PubMed/NCBI
23	Liu P, Zhao H, Wang R, Wang P, Tao Z, Gao L, Yan F, Liu X, Yu S, Ji X and Luo Y: MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress. Stroke. 46:513–519. 2015. View Article : Google Scholar : PubMed/NCBI
24	Dambal S, Shah M, Mihelich B and Nonn L: The microRNA-183 cluster: The family that plays together stays together. Nucleic Acids Res. 43:7173–7188. 2015. View Article : Google Scholar : PubMed/NCBI
25	Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, Horvitz HR, Kauppinen S and Plasterk RH: MicroRNA expression in zebrafish embryonic development. Mechanisms Dev. 122 (Suppl):S149–S150. 2005.
26	Kye MJ, Niederst ED, Wertz MH, Gonçalves Ido C, Akten B, Dover KZ, Peters M, Riessland M, Neveu P, Wirth B, et al: SMN regulates axonal local translation via miR-183/mTOR pathway. Hum Mol Genet. 23:6318–6331. 2014. View Article : Google Scholar : PubMed/NCBI
27	Shi XY, Gu L, Chen J, Guo XR and Shi YL: Downregulation of miR-183 inhibits apoptosis and enhances the invasive potential of endometrial stromal cells in endometriosis. Int J Mol Med. 33:59–67. 2014. View Article : Google Scholar : PubMed/NCBI
28	Sepramaniam S, Jun-Rong T, Kay-Sin T, Deidre Ann De S, Subramaniam T, Fung-Peng W, Chee-Woon W, Fung-Lin Y, Dwi-Setyowati K, Prameet K, et al: Circulating MicroRNAs as Biomarkers of Acute Stroke. Int J Mol Sci. 15:1418–1432. 2014. View Article : Google Scholar : PubMed/NCBI
29	Xiang L, Chen XJ, Wu KC, Zhang CJ, Zhou GH, Lv JN, Sun LF, Cheng FF, Cai XB and Jin ZB: miR-183/96 plays a pivotal regulatory role in mouse photoreceptor maturation and maintenance. Proc Natl Acad Sci USA. 114:6376–6381. View Article : Google Scholar : PubMed/NCBI
30	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
31	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
32	Ito D, Tanaka K, Suzuki S, Dembo T and Fukuuchi Y: Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain. Stroke. 32:1208–1215. 2001. View Article : Google Scholar : PubMed/NCBI
33	Chen J, Yang C, Xu X, Yang Y and Xu B: The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway. Exp Ther Med. 15:897–903. 2018.PubMed/NCBI
34	Ni J, Wang X, Chen S, Liu H, Wang Y, Xu X, Cheng J, Jia J and Zhen X: MicroRNA let-7c-5p protects against cerebral ischemia injury via mechanisms involving the inhibition of microglia activation. Brain Behav Immun. 49:75–85. 2015. View Article : Google Scholar : PubMed/NCBI
35	Wang X, Chen S, Ni J, Cheng J, Jia J and Zhen X: miRNA-3473b contributes to neuroinflammation following cerebral ischemia. Cell Death Dis. 9:112018. View Article : Google Scholar : PubMed/NCBI
36	van der Worp HB, Claus SP, Bär PR, Ramos LM, Algra A, van Gijn J and Kappelle LJ: Reproducibility of measurements of cerebral infarct volume on CT scans. Stroke. 32:424–430. 2001. View Article : Google Scholar : PubMed/NCBI
37	Han M, Choi JW, Rim NJ, Kim SY, Suh HI, Lee KS, Hong JM and Lee JS: Cerebral infarct volume measurements to improve patient selection for endovascular treatment. Medicine (Baltimore). 95:e47022016. View Article : Google Scholar : PubMed/NCBI
38	Imai Y, Ibata I, Ito D, Ohsawa K and Kohsaka S: A novel gene iba1 in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun. 224:855–862. 1996. View Article : Google Scholar : PubMed/NCBI
39	Ohsawa K, Imai Y, Kanazawa H, Sasaki Y and Kohsaka S: Involvement of Iba1 in membrane ruffling and phagocytosis of macrophages/microglia. J Cell Sci. 113:3073–3084. 2000.PubMed/NCBI
40	Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y and Kohsaka S: Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res. 57:1–9. 1998. View Article : Google Scholar : PubMed/NCBI
41	Ito D, Tanaka K, Suzuki S, Dembo T and Fukuuchi Y: Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain. Stroke. 32:1208–1215. 2001. View Article : Google Scholar : PubMed/NCBI
42	Ma Y, Wang J, Wang Y and Yang GY: The biphasic function of microglia in ischemic stroke. Prog Neurobiol. 157:247–272. 2017. View Article : Google Scholar : PubMed/NCBI
43	Rink C and Khanna S: MicroRNA in ischemic stroke etiology and pathology. Physiol Genomics. 43:521–528. 2011. View Article : Google Scholar : PubMed/NCBI
44	Hamzei Taj S, Kho W, Riou A, Wiedermann D and Hoehn M: MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia. Biomaterials. 91:151–165. 2016. View Article : Google Scholar : PubMed/NCBI