Overexpression of miR‑200a‑3p promoted inflammation in sepsis‑induced brain injury through ROS‑induced NLRP3

Yu,Jianhua; Chen,Jinlong; Yang,Hualing; Chen,Sifang; Wang,Zhanxiang

doi:10.3892/ijmm.2019.4326

Overexpression of miR‑200a‑3p promoted inflammation in sepsis‑induced brain injury through ROS‑induced NLRP3

Authors:
- Jianhua Yu
- Jinlong Chen
- Hualing Yang
- Sifang Chen
- Zhanxiang Wang
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Affiliations: Department of ICU, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361000, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361000, P.R. China
Published online on: August 30, 2019 https://doi.org/10.3892/ijmm.2019.4326
Pages: 1811-1823
Copyright : © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Sepsis, a systemic inflammatory response syndrome induced by infection, is a common complication of trauma, burns, postoperative infection and critical disease, and is characterized by an acute onset and high fatality rate. The aim of the present study was to explore the possible molecular mechanisms of microRNA‑200a‑3p (miRNA‑200a‑3p) on inflammation during sepsis. Reverse transcription‑quantitative PCR and gene microarray were used to measure the expression of miRNA‑200a‑3p. Tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 were searched by ELISA. The related proteins expression was measured using western blotting. The expression of miRNA‑200a‑3p was markedly higher in the sepsis model when compared with the normal control group. In addition, the expression of miRNA‑200a‑3p was upregulated by the miRNA‑200a‑3p plasmid in human brain microvascular endothelial cells treated with lipopolysaccharide, which further induced inflammation via the induction of NLR family pyrin domain containing 3 (NLRP3) and suppression of Kelch like ECH associated protein (Keap)‑1/nuclear factor erythroid 2 like 2 (Nrf2)/heme oxygenase (HO)‑1. The inhibition of Keap1/Nrf2/HO‑1 attenuated the effects of anti‑miRNA‑200a‑3p on inflammation. However, the inhibition of NLRP3 attenuated the effects of miRNA‑200a‑3p on inflammation. In conclusion, to the best of our knowledge, the results of the present study demonstrated for the first time that overexpression of miRNA‑200a‑3p promoted inflammation in sepsis‑induced brain injury through reactive oxygen species‑induced NLRP3.

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1	Xie J, Liu JH, Liu H, Liao XZ, Chen Y, Lin MG, Gu YY, Liu TL, Wang DM, Ge H and Mo SL: Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way. BMC Cancer. 16:8992016. View Article : Google Scholar : PubMed/NCBI
2	Wang XT, Lu YX, Sun YH, He WK, Liang JB and Li L: TAK-242 Protects against apoptosis in coronary microem-bolization-induced myocardial injury in rats by suppressing TLR4/NF-kappaB signaling pathway. Cell Physiol Biochem. 41:1675–1683. 2017. View Article : Google Scholar
3	Trojsi F, Christidi F, Migliaccio R, Santamaria-Garcia H and Santangelo G: Behavioural and cognitive changes in neurodegenerative diseases and brain injury. Behav Neurol. 2018.4935915:2018.
4	Huang Z, Shi T, Zhou Q, Shi S, Zhao R, Shi H, Dong L, Zhang C, Zeng K, Chen J and Zhang J: miR-141 Regulates colonic leukocytic trafficking by targeting CXCL12beta during murine colitis and human Crohn's disease. Gut. 63:1247–1257. 2014. View Article : Google Scholar
5	Saito S, Thuc LC, Teshima Y, Nakada C, Nishio S, Kondo H, Fukui A, Abe I, Ebata Y, Saikawa T, et al: Glucose fluctuations aggravate cardiac susceptibility to Ischemia/Reperfusion injury by modulating micrornas expression. Circ J. 80:186–195. 2016. View Article : Google Scholar
6	Roberts RL, Topless RK, Phipps-Green AJ, Gearry RB, Barclay ML and Merriman TR: Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease. Genes Immun. 11:351–356. 2010. View Article : Google Scholar : PubMed/NCBI
7	Dong YF, Chen ZZ, Zhao Z, Yang DD, Yan H, Ji J and Sun XL: Potential role of microRNA-7 in the anti-neuroinflammation effects of nicorandil in astrocytes induced by oxygen-glucose deprivation. J Neuroinflammation. 13:602016. View Article : Google Scholar : PubMed/NCBI
8	Liu HL, Wei YJ, Jin ZG, Zhang J, Ding P, Yang SL, Luo JP, Ma DX, Liu Y and Han W: Design and rationale of the APELOT trial: A randomized, open-label, multicenter, phase IV study to evaluate the antiplatelet effect of different loading dose of ticagrelor in patients with non-st acute coronary syndrome undergoing percutaneous coronary intervention. Medicine (Baltimore). 95:e37562016. View Article : Google Scholar
9	Zhang QS, Liu W and Lu GX: miR-200a-3p promotes b-Amyloid-induced neuronal apoptosis through down-regulation of SIRT1 in Alzheimer's disease. J Biosci. 42:397–404. 2017. View Article : Google Scholar
10	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
11	Yang ML, Li JJ, So KF, Chen JY, Cheng WS, Wu J, Wang ZM, Gao F and Young W: Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: A double-blind, randomized, placebo-controlled clinical trial. Spinal Cord. 50:141–146. 2012. View Article : Google Scholar
12	Lin C, Liu Z, Lu Y, Yao Y, Zhang Y, Ma Z, Kuai M, Sun X, Sun S, Jing Y, et al: Cardioprotective effect of Salvianolic acid B on acute myocardial infarction by promoting autophagy and neovascularization and inhibiting apoptosis. J Pharm Pharmacol. 68:941–952. 2016. View Article : Google Scholar : PubMed/NCBI
13	Cai L, Wang H and Yang Q: CRKL overexpression promotes cell proliferation and inhibits apoptosis in endometrial carcinoma. Oncol Lett. 13:51–56. 2017. View Article : Google Scholar : PubMed/NCBI
14	Singh SK, Banerjee S, Acosta EP, Lillard JW and Singh R: Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/p21WAF1/CIP1 and p27KIP1 pathway. Oncotarget. 8:17216–17228. 2017. View Article : Google Scholar : PubMed/NCBI
15	Lee Y, Kim E, Kim BK and Shin JH: A case of successful reperfusion through a combination of intracoronary thrombolysis and aspiration thrombectomy in ST-segment elevation myocardial infarction associated with an ectatic coronary artery. BMC Cardiovasc Disord. 17:942017. View Article : Google Scholar : PubMed/NCBI
16	Gwag HB, Kim EK, Park TK, Lee JM, Yang JH, Song YB, Choi JH, Choi SH, Lee SH, Chang SA, et al: Cardioprotective effects of intracoronary morphine in ST-Segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: A prospective, randomized trial. J Am Heart Assoc. 6:e0054262017. View Article : Google Scholar : PubMed/NCBI
17	Dalmau Llorca MR, Goncalves AQ and Forcadell Drago E: Fernández-Sáez J, Hernández Rojas Z, Pepió Vilaubí JM, Rodríguez Cumplido D, Morral Parente RM and Aguilar Martín C: A new clinical decision support tool for improving the adequacy of anticoagulant therapy and reducing the incidence of stroke in nonvalvular atrial fibrillation: A randomized clinical trial in primary care. Medicine (Baltimore). 97:e95782018. View Article : Google Scholar
18	Khan MT, Ikram A, Saeed O, Afridi T, Sila CA, Smith MS, Irshad K and Shuaib A: Deep vein thrombosis in acute stroke-a systemic review of the literature. Cureus. 9:e19822017.
19	Xiao Y, Yan W, Lu L, Wang Y, Lu W, Cao Y and Cai W: p38/p53/miR-200a-3p feedback loop promotes oxidative stress-mediated liver cell death. Cell Cycle. 14:1548–1558. 2015. View Article : Google Scholar : PubMed/NCBI
20	Costa CL, Spilborghs GM, Martins MA, Saldiva PH and Mauad T: Nitric acid-induced bronchiolitis in rats mimics childhood Bronchiolitis obliterans. Respiration. 72:642–649. 2005. View Article : Google Scholar : PubMed/NCBI
21	Ding XQ, Wu WY, Jiao RQ, Gu TT, Xu Q, Pan Y and Kong LD: Curcumin and allopurinol ameliorate fructose-induced hepatic inflammation in rats via miR-200a-mediated TXNIP/NLRP3 inflammasome inhibition. Pharmacol Res. 137:64–75. 2018. View Article : Google Scholar : PubMed/NCBI
22	Sadaka F, Jadhav A, O'Brien J and Trottier S: Do all acute stroke patients receiving tPA require ICU Admission? J Clin Med Res. 10:174–177. 2018. View Article : Google Scholar : PubMed/NCBI
23	Alhazzani AA, Mahfouz AA, Abolyazid AY, Awadalla NJ, Aftab R, Faraheen A and Khalil SN: Study of stroke incidence in the aseer region,. Southwestern Saudi Arabia Int J Environ Res Public Health. 15:E2152018. View Article : Google Scholar
24	Wei J, Zhang Y, Luo Y, Wang Z, Bi S, Song D, Dai Y, Wang T, Qiu L, Wen L, et al: Aldose reductase regulates miR-200a-3p/141-3p to coordinate Keap1-Nrf2, Tgfb1/2, and Zeb1/2 signaling in renal mesangial cells and the renal cortex of diabetic mice. Free Radic Biol Med. 67:91–102. 2014. View Article : Google Scholar