MicroRNA‑21 inhibits lipopolysaccharide‑induced acute lung injury by targeting nuclear factor‑κB

Zhu,Wei‑Dong; Xu,Jia; Zhang,Mao; Zhu,Tie‑Ming; Zhang,Yun‑Hua; Sun,Ke

doi:10.3892/etm.2018.6789

MicroRNA‑21 inhibits lipopolysaccharide‑induced acute lung injury by targeting nuclear factor‑κB

Authors:
- Wei‑Dong Zhu
- Jia Xu
- Mao Zhang
- Tie‑Ming Zhu
- Yun‑Hua Zhang
- Ke Sun
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Affiliations: Emergency Department, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Personnel Section, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Emergency Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China, Hepatobiliary Surgery Department, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Intensive Care Unit, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China, Orthopedics Department, Traditional Chinese Medical Hospital of Zhuji, Zhuji, Zhejiang 311800, P.R. China
Published online on: September 24, 2018 https://doi.org/10.3892/etm.2018.6789
Pages: 4616-4622
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA‑21 (miR‑21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6, IL‑1β and IL‑10, and the level of miR‑21 expression were measured in the lungs of LPS‑induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR‑21 in the inﬂammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR‑21 or an anti‑miR‑21 inhibitor, and the subsequent changes of the miR‑21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS‑induced ALI in rats resulted in significant overexpression of pro‑inﬂammatory cytokines, TNF‑α, IL‑6 and IL‑1β, and miR‑21, but reduced the expression of the anti‑inﬂammatory cytokine IL‑10. LPS treatment also led to a higher expression level of miR‑21 and increased secretion of pro‑inﬂammatory cytokines in NR8383 cells in a time‑dependent manner. Manipulation with the miR‑21 mimic significantly suppressed the LPS‑mediated induction of TNF‑α, IL‑6 and IL‑1β in NR8383 cells, while that induction was upregulated when miR‑21 expression was silenced via transfection with the anti‑miR‑21 inhibitor. Further mechanism experiments revealed that miR‑21 regulates LPS‑induced inflammation responses via the Toll‑like receptor 4 and nuclear factor‑κB (Nf‑κB) signaling pathway. miR‑21 negatively regulates inflammatory responses in LPS‑induced ALI by targeting the NF‑κB signaling pathway, providing further insight into the molecular mechanism of ALI progression.

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1	Guo Z, Gu Y, Wang C, Zhang J, Shan S, Gu X, Wang K, Han Y and Ren T: Enforced expression of miR-125b attenuates LPS-induced acute lung injury. Immunol Lett. 162:18–26. 2014. View Article : Google Scholar : PubMed/NCBI
2	Xu Z, Zhang C, Cheng L, Hu M, Tao H and Song L: The microRNA miR-17 regulates lung FoxA1 expression during lipopolysaccharide-induced acute lung injury. Biochem Biophys Res Commun. 445:48–53. 2014. View Article : Google Scholar : PubMed/NCBI
3	Zhao J, Li X, Zou M, He J, Han Y, Wu D, Yang H and Wu J: miR-135a inhibition protects A549 cells from LPS-induced apoptosis by targeting Bcl-2. Biochem Biophys Res Commun. 452:951–957. 2014. View Article : Google Scholar : PubMed/NCBI
4	Chen XY, Dou YX, Luo DD, Zhang ZB, Li CL, Zeng HF, Su ZR, Xie JH, Lai XP and Li YC: β-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-κB and activating Nrf2 pathways. Int Immunopharmacol. 50:270–278. 2017. View Article : Google Scholar : PubMed/NCBI
5	Song L, Zhou F, Cheng L, Hu M, He Y, Zhang B, Liao D and Xu Z: MicroRNA-34a suppresses autophagy in alveolar type II epithelial cells in acute lung injury by inhibiting FoxO3 expression. Inflammation. 40:927–936. 2017. View Article : Google Scholar : PubMed/NCBI
6	Li W, Qiu X, Jiang H, Han Y, Wei D and Liu J: Downregulation of miR-181a protects mice from LPS-induced acute lung injury by targeting Bcl-2. Biomed Pharmacother. 84:1375–1382. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zeng Z, Gong H, Li Y, Jie K, Ding C, Shao Q, Liu F, Zhan Y, Nie C, Zhu W and Qian K: Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury. Exp Lung Res. 39:275–282. 2013. View Article : Google Scholar : PubMed/NCBI
8	Li W, Ma K, Zhang S, Zhang H, Liu J, Wang X and Li S: Pulmonary microRNA expression profiling in an immature piglet model of cardiopulmonary bypass-induced acute lung injury. Artif Organs. 39:327–335. 2015. View Article : Google Scholar : PubMed/NCBI
9	Lee SM, Choi H, Yang G, Park KC, Jeong S and Hong S: microRNAs mediate oleic acid-induced acute lung injury in rats using an alternative injury mechanism. Mol Med Rep. 10:292–300. 2014. View Article : Google Scholar : PubMed/NCBI
10	Tao Z, Yuan Y and Liao Q: Alleviation of lipopolysaccharides-induced acute lung injury by miR-454. Cell Physiol Biochem. 38:65–74. 2016. View Article : Google Scholar : PubMed/NCBI
11	Wang W, Liu Z, Su J, Chen WS, Wang XW, Bai SX, Zhang JZ and Yu SQ: Macrophage micro-RNA-155 promotes lipopolysaccharide-induced acute lung injury in mice and rats. Am J Physiol Lung Cell Mol Physiol. 311:L494–L506. 2016. View Article : Google Scholar : PubMed/NCBI
12	Feng J, Li A, Deng J, Yang Y, Dang L, Ye Y, Li Y and Zhang W: miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: Potential role in cerebrovascular disease. Lipids Health Dis. 13:272014. View Article : Google Scholar : PubMed/NCBI
13	Lu Z, Zuo B, Jing R, Gao X, Rao Q, Liu Z, Qi H, Guo H and Yin H: Dendritic cell-derived exosomes elicit tumor regression in autochthonous hepatocellular carcinoma mouse models. J Hepatol. 67:739–748. 2017. View Article : Google Scholar : PubMed/NCBI
14	Li H, Jia Z, Li A, Jenkins G, Yang X, Hu J and Guo W: Resveratrol repressed viability of U251 cells by miR-21 inhibiting of NF-κB pathway. Mol Cell Biochem. 382:137–143. 2013. View Article : Google Scholar : PubMed/NCBI
15	Zhong X, Chung AC, Chen HY, Dong Y, Meng XM, Li R, Yang W, Hou FF and Lan HY: miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia. 56:663–674. 2013. View Article : Google Scholar : PubMed/NCBI
16	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
17	Wei C, Li L, Kim IK, Sun P and Gupta S: NF-κB mediated miR-21 regulation in cardiomyocytes apoptosis under oxidative stress. Free Radic Res. 48:282–291. 2014. View Article : Google Scholar : PubMed/NCBI
18	Chen Y, Xian PF, Yang L and Wang SX: MicroRNA-21 promotes proliferation of fibroblast-like synoviocytes through mediation of NF-κB nuclear translocation in a rat model of collagen-induced rheumatoid arthritis. Biomed Res Int. 2016:92790782016.PubMed/NCBI
19	Tang R, Pei L, Bai T and Wang J: Down-regulation of microRNA-126-5p contributes to overexpression of VEGFA in lipopolysaccharide-induced acute lung injury. Biotechnol Lett. 38:1277–1284. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhao J, Chen C, Guo M, Tao Y, Cui P, Zhou Y, Qin N, Zheng J, Zhang J and Xu L: MicroRNA-7 deficiency ameliorates the pathologies of acute lung injury through elevating KLF4. Front Immunol. 7:3892016. View Article : Google Scholar : PubMed/NCBI
21	Chen C, Luo F, Liu X, Lu L, Xu H, Yang Q, Xue J, Shi L, Li J, Zhang A and Liu Q: NF-κB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis. Cancer Lett. 388:21–33. 2017. View Article : Google Scholar : PubMed/NCBI
22	Wang Y, Mao G, Lv Y, Huang Q and Wang G: MicroRNA-181b stimulates inflammation via the nuclear factor-κB signaling pathway in vitro. Exp Ther Med. 10:1584–1590. 2015. View Article : Google Scholar : PubMed/NCBI
23	Wang J, Bai X, Song Q, Fan F, Hu Z, Cheng G and Zhang Y: miR-223 inhibits lipid deposition and inflammation by suppressing toll-like receptor 4 signaling in macrophages. Int J Mol Sci. 16:24965–24982. 2015. View Article : Google Scholar : PubMed/NCBI
24	Zhou Z and You Z: Mesenchymal stem cells alleviate LPS-induced acute lung injury in mice by miR-142a-5p-controlled pulmonary endothelial cell autophagy. Cell Physiol Biochem. 38:258–266. 2016. View Article : Google Scholar : PubMed/NCBI
25	Lee HM, Kim TS and Jo EK: miR-146 and miR-125 in the regulation of innate immunity and inflammation. BMB Rep. 49:311–318. 2016. View Article : Google Scholar : PubMed/NCBI
26	Bao MH, Li JM, Luo HQ, Tang L, Lv QL, Li GY and Zhou HH: NF-κB-regulated miR-99a modulates endothelial cell inflammation. Mediators Inflamm. 2016:53081702016. View Article : Google Scholar : PubMed/NCBI
27	Zhang D, Cao X, Li J and Zhao G: miR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis. Sci Rep. 5:127752015. View Article : Google Scholar : PubMed/NCBI
28	Xiao J, Tang J, Chen Q, Tang D, Liu M, Luo M, Wang Y, Wang J, Zhao Z, Tang C, et al: miR-429 regulates alveolar macrophage inflammatory cytokine production and is involved in LPS-induced acute lung injury. Biochem J. 471:281–291. 2015. View Article : Google Scholar : PubMed/NCBI
29	Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O'Leary JJ, Ruan Q, Johnson DS, Chen Y and O'Neill LA: Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 11:141–147. 2010. View Article : Google Scholar : PubMed/NCBI
30	Peng P, Li Z and Liu X: Reduced expression of miR-23a suppresses A20 in TLR-stimulated macrophages. Inflammation. 38:1787–1793. 2015. View Article : Google Scholar : PubMed/NCBI