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BMC Pulmonary Medicine
Published in: BMC Pulmonary Medicine 1/2021

01-12-2021 | Acute Respiratory Distress-Syndrome | Research

Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

Authors: Qingsong Sun, Man Luo, Zhiwei Gao, Xiang Han, Weiqin Wu, Hongmei Zhao

Published in: BMC Pulmonary Medicine | Issue 1/2021

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Abstract

Background

Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI.

Methods

We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI.

Result

TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis.

Conclusion

OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.
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Literature
1.
Mahadeo KM, Bajwa R, Abdel-Azim H, Lehmann LE, Duncan C, Zantek N, et al. Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement. Lancet Haematol. 2020;7(1):e61–72.PubMedCrossRef
2.
Ho MS, Mei SH, Stewart DJ. The immunomodulatory and therapeutic effects of mesenchymal stromal cells for acute lung injury and sepsis. J Cell Physiol. 2015;230(11):2606–17.PubMedCrossRef
3.
Favarin DC, de Oliveira JR, de Oliveira CJ, Rogerio Ade P. Potential effects of medicinal plants and secondary metabolites on acute lung injury. BioMed Res Int. 2013;2013:576479.PubMed
4.
Sadowitz B, Roy S, Gatto LA, Habashi N, Nieman G. Lung injury induced by sepsis: lessons learned from large animal models and future directions for treatment. Expert Rev Anti Infect Ther. 2011;9(12):1169–78.PubMedCrossRef
5.
Shin NR, Park SH, Ko JW, Ryu HW, Jeong SH, Kim JC, et al. Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced acute lung injury model. Lab Anim Res. 2017;33(3):209–15.PubMedPubMedCentralCrossRef
6.
Ali FF, Abdel-Hamid HA, Toni ND. H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats. Gen Physiol Biophys. 2018;37:421–31.CrossRef
7.
Song C, Li H, Li Y, Dai M, Zhang L, Liu S, et al. NETs promote ALI/ARDS inflammation by regulating alveolar macrophage polarization. Exp Cell Res. 2019;382(2):111486.PubMedCrossRef
8.
Lou J, Hu Y, Wu MD, Che LQ, Wu YF, Zhao Y, et al. Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury. Acta Pharmacol Sin. 2019;40(6):769–80.PubMedCrossRef
9.
Guo RF, Ward PA. Role of oxidants in lung injury during sepsis. Antioxid Redox Signal. 2007;9(11):1991–2002.PubMedCrossRef
10.
Vishnubalaji R, Shaath H, Elango R, Alajez NM. Noncoding RNAs as potential mediators of resistance to cancer immunotherapy. Semin Cancer Biol. 2020;65:65–79.PubMedCrossRef
11.
Zhao Z, Sun W, Guo Z, Zhang J, Yu H, Liu B. Mechanisms of lncRNA/microRNA interactions in angiogenesis. Life Sci. 2020;254:116900.PubMedCrossRef
12.
Zhang XZ, Liu H, Chen SR. Mechanisms of long non-coding RNAs in cancers and their dynamic regulations. Cancers. 2020;12(5):1245.PubMedCentralCrossRef
13.
14.
Abdollahzadeh R, Daraei A, Mansoori Y, Sepahvand M, Amoli MM, Tavakkoly-Bazzaz J. Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: a new look at hallmarks of breast cancer. J Cell Physiol. 2019;234(7):10080–100.PubMedCrossRef
15.
Jiang Y, Zhu F, Wu GS, Wang KA, Wang C, Yu Q, et al. Microarray and bioinformatics analysis of circular RNAs expression profile in traumatic lung injury. Exp Ther Med. 2020;20(1):227–34.PubMedPubMedCentralCrossRef
16.
Zhou Z, Zhu Y, Gao G, Zhang Y. Long noncoding RNA SNHG16 targets miR-146a-5p/CCL5 to regulate LPS-induced WI-38 cell apoptosis and inflammation in acute pneumonia. Life Sci. 2019;228:189–97.PubMedCrossRef
17.
Zhang Y, Zhu Y, Gao G, Zhou Z. Knockdown XIST alleviates LPS-induced WI-38 cell apoptosis and inflammation injury via targeting miR-370-3p/TLR4 in acute pneumonia. Cell Biochem Funct. 2019;37(5):348–58.PubMedPubMedCentralCrossRef
18.
Li H, Shi H, Gao M, Ma N, Sun R. Long non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis. Cell Biosci. 2018;8:15.PubMedPubMedCentralCrossRef
19.
Ma YS, Chu KJ, Ling CC, Wu TM, Zhu XC, Liu JB, et al. Long noncoding RNA OIP5-AS1 promotes the progression of liver hepatocellular carcinoma via regulating the hsa-miR-26a-3p/EPHA2 axis. Mol Ther Nucleic Acids. 2020;21:229–41.PubMedPubMedCentralCrossRef
20.
Chen X, Xiong D, Yang H, Ye L, Mei S, Wu J, et al. Long noncoding RNA OPA-interacting protein 5 antisense transcript 1 upregulated SMAD3 expression to contribute to metastasis of cervical cancer by sponging miR-143-3p. J Cell Physiol. 2019;234(4):5264–75.PubMedCrossRef
21.
Niu X, Pu S, Ling C, Xu J, Wang J, Sun S, et al. lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway. Cell Prolif. 2020;53(6):e12818.PubMedPubMedCentralCrossRef
22.
Zhi L, Zhao J, Zhao H, Qing Z, Liu H, Ma J. Downregulation of LncRNA OIP5-AS1 induced by IL-1β aggravates osteoarthritis via regulating miR-29b-3p/PGRN. Cartilage. 2020:1947603519900801.
23.
Qing P, Liu Y. Inhibitory role of long non-coding RNA OIP5-AS1 in rheumatoid arthritis progression through the microRNA-448-paraoxonase 1-toll-like receptor 3-nuclear factor κB axis. Exp Physiol. 2020;105:1708–19.PubMedCrossRef
24.
Ren M, Wang T, Han Z, Fu P, Liu Z, Ouyang C. LncRNA OIP5-AS1 contributes to the progression of atherosclerosis by targeting miR-26a-5p through AKT/NF-κB pathway. J Cardiovasc Pharmacol. 2020;76:635–44.PubMedCrossRef
25.
Machackova T, Mlcochova H, Stanik M, Dolezel J, Fedorko M, Pacik D, et al. MiR-429 is linked to metastasis and poor prognosis in renal cell carcinoma by affecting epithelial-mesenchymal transition. Tumour Biol. 2016;37(11):14653–8.PubMedCrossRef
26.
27.
Fan JL, Zhang L, Bo XH. MiR-126 on mice with coronary artery disease by targeting S1PR2. Eur Rev Med Pharmacol Sci. 2020;24(2):893–904.PubMed
28.
Li Y, Huang J, Yan H, Li X, Ding C, Wang Q, et al. Protective effect of microRNA381 against inflammatory damage of endothelial cells during coronary heart disease by targeting CXCR4. Mol Med Rep. 2020;21:1439–48.PubMedPubMedCentral
29.
Zhang W, Chen L, Jiang Y, Shen Y. miR-26a-5p regulates synovial fibroblast invasion in patients with rheumatoid arthritis by targeting smad 1. Med Sci Monit. 2018;24:5178–84.PubMedPubMedCentralCrossRef
30.
Zhang Y, Su Z, Liu HL, Li L, Wei M, Ge DJ, et al. Effects of miR-26a-5p on neuropathic pain development by targeting MAPK6 in in CCI rat models. Biomed Pharmacother. 2018;107:644–9.PubMedCrossRef
31.
Zuniga MC, Raghuraman G, Hitchner E, Weyand C, Robinson W, Zhou W. PKC-epsilon and TLR4 synergistically regulate resistin-mediated inflammation in human macrophages. Atherosclerosis. 2017;259:51–9.PubMedPubMedCentralCrossRef
32.
Zusso M, Lunardi V, Franceschini D, Pagetta A, Lo R, Stifani S, et al. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J Neuroinflammation. 2019;16(1):148.PubMedPubMedCentralCrossRef
33.
Hu L, Yang H, Ai M. Inhibition of TLR4 alleviates the inflammation and apoptosis of retinal ganglion cells in high glucose. Graefes Arch Clin Exp Ophthalmol. 2017;255(11):2199–210.PubMedCrossRef
34.
Gonzalez-Guerrero C, Cannata-Ortiz P, Guerri C, Egido J, Ortiz A, Ramos AM. TLR4-mediated inflammation is a key pathogenic event leading to kidney damage and fibrosis in cyclosporine nephrotoxicity. Arch Toxicol. 2017;91(4):1925–39.PubMedCrossRef
35.
Nayak DK, Mendez O, Bowen S, Mohanakumar T. Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages. J Vis Exp. 2018; (134):57287.
36.
Wang H, Fan J, Li NL, Li JT, Yuan SF, Yi J, et al. A subanesthetic dose of isoflurane during postconditioning ameliorates zymosan-induced neutrophil inflammation lung injury and mortality in mice. Mediators Inflamm. 2013;2013:479628.PubMedPubMedCentral
37.
van Lieshout LP, Domm JM, Wootton SK. AAV-mediated gene delivery to the lung. Methods Mol Biol. 2019;1950:361–72.PubMedCrossRef
38.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402–8.CrossRefPubMed
39.
Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR. Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. J Vis Exp. 2011; (50):2597.
40.
Ding XM, Pan L, Wang Y, Xu QZ. Baicalin exerts protective effects against lipopolysaccharide-induced acute lung injury by regulating the crosstalk between the CX3CL1-CX3CR1 axis and NF-kappaB pathway in CX3CL1-knockout mice. Int J Mol Med. 2016;37(3):703–15.PubMedPubMedCentralCrossRef
41.
Engelmann C, Sheikh M, Sharma S, Kondo T, Loeffler-Wirth H, Zheng YB, et al. Toll-like receptor 4 is a therapeutic target for prevention and treatment of liver failure. J Hepatol. 2020;73(1):102–12.PubMedCrossRef
42.
Takizawa H, Fritsch K, Kovtonyuk LV, Saito Y, Yakkala C, Jacobs K, et al. Pathogen-induced TLR4-TRIF innate immune signaling in hematopoietic stem cells promotes proliferation but reduces competitive fitness. Cell Stem Cell. 2017;21(2):225-40.e5.CrossRefPubMed
43.
Takizawa H, Fritsch K, Kovtonyuk LV, Saito Y, Yakkala C, Jacobs K, et al. Pathogen-induced TLR4-TRIF innate immune signaling in hematopoietic stem cells promotes proliferation but reduces competitive fitness. Cell Stem Cell. 2020;27(1):177.PubMedCrossRef
44.
Kayagaki N, Wong MT, Stowe IB, Ramani SR, Gonzalez LC, Akashi-Takamura S, et al. Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science. 2013;341(6151):1246–9.PubMedCrossRef
45.
Bachmaier K, Toya S, Gao X, Triantafillou T, Garrean S, Park GY, et al. E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury. Nat Med. 2007;13(8):920–6.PubMedCrossRef
46.
Tauseef M, Knezevic N, Chava KR, Smith M, Sukriti S, Gianaris N, et al. TLR4 activation of TRPC6-dependent calcium signaling mediates endotoxin-induced lung vascular permeability and inflammation. J Exp Med. 2012;209(11):1953–68.PubMedPubMedCentralCrossRef
47.
Yamada M, Kubo H, Kobayashi S, Ishizawa K, He M, Suzuki T, et al. The increase in surface CXCR4 expression on lung extravascular neutrophils and its effects on neutrophils during endotoxin-induced lung injury. Cell Mol Immunol. 2011;8(4):305–14.PubMedPubMedCentralCrossRef
48.
Huang X, Xiu H, Zhang S, Zhang G. The Role of Macrophages in the Pathogenesis of ALI/ARDS. Mediators Inflamm. 2018;2018:1264913.PubMedPubMedCentral
49.
Lakhia R, Yheskel M, Flaten A, Ramalingam H, Aboudehen K, Ferrè S, et al. Interstitial microRNA miR-214 attenuates inflammation and polycystic kidney disease progression. JCI insight. 2020;5(7):e133785.PubMedCentralCrossRef
50.
Wu G, Zhou W, Lin X, Sun Y, Li J, Xu H, et al. circRASSF2 Acts as ceRNA and promotes papillary thyroid carcinoma progression through miR-1178/TLR4 signaling pathway. Mol Ther Acids. 2020;19:1153–63.CrossRef
51.
Sen R, Ghosal S, Das S, Balti S, Chakrabarti J. Competing endogenous RNA: the key to posttranscriptional regulation. ScientificWorldJournal. 2014;2014:896206.PubMedPubMedCentralCrossRef
52.
53.
Wang HR, Guo XY, Liu XY, Song X. Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axis. Inflamm Res. 2020;69(6):559–68.PubMedCrossRef
Metadata
Title
Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis
Authors
Qingsong Sun
Man Luo
Zhiwei Gao
Xiang Han
Weiqin Wu
Hongmei Zhao
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2021
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-021-01589-1

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