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BMC Complementary Medicine and Therapies

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Open Access 01-12-2020 | Pneumonia | Research article

The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus

Authors: Ke Li, Xiaoming Chen, Jing Zhong, Hehe Ye, Shujing Zhang, Dongyu Ge, Xudan Wang, Ying Wu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Abstract

Background

MicroRNAs (miRNAs) play vital roles in acute inflammatory and antiviral responses during influenza A virus (IAV) infection. The Xijiao Dihuang decoction combined with Yinqiao powder (XDY) is applied to remedy viral pneumonia in China and its therapeutic efficacy in pneumonic mice challenged with IAV was demonstrated; however, the underlying mechanisms remain elusive. Thus, this study aimed to explore the miRNA-mRNA profiles in the lungs of IAV-infected mice and investigate the therapeutic mechanisms of XDY involving miRNAs and associated pathways.

Methods

We detected the cellular miRNA contents in the lungs of mice treated with XDY (23 g/kg/d) for A/FM/1/47 (H1N1) (FM1) infection at 4 days postinoculation (dpi) and 7 dpi. MiRNA and mRNA high-throughput sequencing analyses, and miRNA and mRNA qRT-PCR analyses were used to detect and verify the relevant miRNAs and mRNAs. Conjoint analysis, GO enrichment analysis, and KEGG database analysis were applied to identify the miRNA-mRNA regulatory relationships.

Results

The quantities of differentially expressed miRNAs and mRNAs were upregulated over time. The data showed that 104 miRNAs and 3485 mRNAs were differentially expressed after challenge with FM1 on day 4, while 191 miRNAs and 6126 mRNAs were differentially expressed on day 7. The GO enrichment analysis and KEGG database data showed that the differentially expressed miRNAs and mRNAs were mainly enriched in JNK activity, MAPK phosphatase activity, and the TLR, Jak-STAT and TNF signalling pathways after treatment of FM1 infection with XDY. Generally, the expression trends of differentially expressed miRNAs and mRNAs based on the qRT-PCR results exhibited good consistency with the results of the high-throughput sequencing analysis.

Conclusions

MiRNAs and mRNAs were differentially expressed during FM1 infection. The therapeutic mechanisms of XDY in FM1-infected mice, might be related to regulating antiviral immunity and ameliorating excessive inflammatory responses by modulating the expression of dysregulated miRNAs and mRNAs involved in the ERK/JNK-AP-1, and IFN-β/STAT signalling pathways.

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Pociask DA, Robinson KM, Chen K, McHugh KJ, Clay ME, Huang GT, Benos PV, Janssen-Heininger Y, Kolls JK, Anathy V, et al. Epigenetic and transcriptomic regulation of lung repair during recovery from influenza infection. Am J Pathol. 2017;187(4):851–63.PubMedPubMedCentralCrossRef

Price I, Mochan-Keef ED, Swigon D, Ermentrout GB, Lukens S, Toapanta FR, Ross TM, Clermont G. The inflammatory response to influenza a virus (H1N1): An experimental and mathematical study. J Theor Biol. 2015;374:83–93.PubMedPubMedCentralCrossRef

Tate MD, Brooks AG, Reading PC. Inhibition of lectin-mediated innate host defences in vivo modulates disease severity during influenza virus infection. Immunol Cell Biol. 2011;89(3):482–91.PubMedCrossRef

Li Y, Chan EY, Li J, Ni C, Peng X, Rosenzweig E, Tumpey TM, Katze MG. MicroRNA expression and virulence in pandemic influenza virus-infected mice. J Virol. 2010;84(6):3023–32.PubMedPubMedCentralCrossRef

Wang B, Jiang L, Xu Q. Comprehensive assessment for miRNA polymorphisms in hepatocellular cancer risk: a systematic review and meta-analysis. BIOSCIENCE REP. 2018;38(5):R20180712.CrossRef

Zhu Z, Qi Y, Ge A, Zhu Y, Xu K, Ji H, Shi Z, Cui L, Zhou M. Comprehensive characterization of serum MicroRNA profile in response to the emerging avian influenza a (H7N9) virus infection in humans. Viruses. 2014;6(4):1525–39.PubMedPubMedCentralCrossRef

Huang L, Ma J, Sun Y, Lv Y, Lin W, Liu M, Tu C, Zhou P, Gu W, Su S, et al. Altered splenic miRNA expression profile in H1N1 swine influenza. Arch Virol. 2015;160(4):979–85.PubMedCrossRef

Zhao F, Su S, Zhou D, Zhou P, Xu T, Zhang L, Cao N, Qi W, Zhang G, Li S. Comparative analysis of microRNAs from the lungs and trachea of dogs (Canis familiaris) infected with canine influenza virus. Infect Genet Evol. 2014;21:367–74.PubMedCrossRef

Moran J, Ramirez-Martinez G, Jimenez-Alvarez L, Cruz A, Perez-Patrigeon S, Hidalgo A, Orozco L, Martinez A, Padilla-Noriega L, Avila-Moreno F, et al. Circulating levels of miR-150 are associated with poorer outcomes of a/H1N1 infection. Exp Mol Pathol. 2015;99(2):253–61.PubMedCrossRef

10.

Wu Z, Hao R, Li P, Zhang X, Liu N, Qiu S, Wang L, Wang Y, Xue W, Liu K, et al. MicroRNA expression profile of mouse lung infected with 2009 pandemic H1N1 influenza virus. PLoS One. 2013;8(9):e74190.PubMedPubMedCentralCrossRef

11.

Loveday EK, Svinti V, Diederich S, Pasick J, Jean F. Temporal- and strain-specific host microRNA molecular signatures associated with swine-origin H1N1 and avian-origin H7N7 influenza a virus infection. J Virol. 2012;86(11):6109–22.PubMedPubMedCentralCrossRef

12.

Terrier O, Textoris J, Carron C, Marcel V, Bourdon JC, Rosa-Calatrava M. Host microRNA molecular signatures associated with human H1N1 and H3N2 influenza a viruses reveal an unanticipated antiviral activity for miR-146a. J Gen Virol. 2013;94(Pt 5):985–95.PubMedCrossRef

13.

Choi EJ, Kim HB, Baek YH, Kim EH, Pascua PN, Park SJ, Kwon HI, Lim GJ, Kim S, Kim YI, et al. Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus. BMC Microbiol. 2014;14:252.PubMedPubMedCentralCrossRef

14.

Li Y, Li J, Belisle S, Baskin CR, Tumpey TM, Katze MG. Differential microRNA expression and virulence of avian, 1918 reassortant, and reconstructed 1918 influenza a viruses. Virology. 2011;421(2):105–13.PubMedPubMedCentralCrossRef

15.

Fu YJ, Yan YQ, Zheng X, Shi SS, Wu S, Jiang ZY. Effects of Xinjiaxiangruyin on the TLR7 pathway in influenza virus-infected lungs of mice housed in a hygrothermal environment. Chin Med. 2019;14:39.PubMedPubMedCentralCrossRef

16.

Liu J, Mei W, Li Y, Wang E, Ji L, Tao P. Antiviral activity of mixed-valence rare earth borotungstate heteropoly blues against influenza virus in mice. Antivir Chem Chemother. 2000;11(6):367–72.PubMedCrossRef

17.

Lofstrom G, Oker-Blom N. Comparison between an American, a Dutch and a Swedish strain of influenza virus a isolated in 1947. Acta Med Scand. 1949;134(3):232–4.PubMedCrossRef

18.

Meiklehjohn G, Bruyn HB. Influenza in California during 1947 and 1948. Am J Public Health Nations Health. 1949;39(1):44–9.CrossRef

19.

Zheng X, Fu Y, Shi SS, Wu S, Yan Y, Xu L, Wang Y, Jiang Z. Effect of Forsythiaside a on the RLRs signaling pathway in the lungs of mice infected with the influenza a virus FM1 strain. Molecules. 2019;24(23):4219.

20.

Zhong J, Cui X, Shi Y, Gao Y, Cao H. Antiviral activity of Jinchai capsule against influenza virus. J Tradit Chin Med. 2013;33(2):200–4.PubMedCrossRef

21.

Zhong Y, Zhou J, Liang N, Liu B, Lu R, He Y, Liang C, Wu J, Zhou Y, Hu M, et al. Effect of maxing Shigan Tang on H1N1 influenza a virus-associated acute lung injury in mice. Intervirology. 2016;59(5–6):267–74.PubMedCrossRef

22.

Liu YM, Zhu LL, Li R, Zhang JL, Yao SS, Zhou XB, Zeng H, Wang XB. Xijiao Dihuang decoction () and Rehmannia glutinosa Libosch. Protect mice against lipopolysaccharide and tumor necrosis factor alpha-induced acute liver failure. Chin J Integr Med. 2019;25(6):446–53.PubMedCrossRef

23.

Lu J, Yan J, Yan J, Zhang L, Chen M, Chen Q, Cheng L, Li P. Network pharmacology based research into the effect and mechanism of Xijiao Dihuang decoction against sepsis. Biomed Pharmacother. 2020;122:109777.PubMedCrossRef

24.

Wang YG, Gao Y, Feng J, Dou YQ. Effect of modified Xijiao Dihuang decoction () on intestinal Flora and Th17/Treg in rats with radiation enteritis. Chin J Integr Med. 2020. https://doi.org/10.1007/s11655-020-3261-x.

25.

Li C. The treatment of viral pneumonia with modified Xijiao Dihuang decoction. Heilongjiang J Tradit Chin. 2001;06:42.

26.

Fu YJ, Yan YQ, Qin HQ, Wu S, Shi SS, Zheng X, Wang PC, Chen XY, Tang XL, Jiang ZY. Effects of different principles of traditional Chinese medicine treatment on TLR7/NF-kappaB signaling pathway in influenza virus infected mice. Chin Med. 2018;13:42.PubMedPubMedCentralCrossRef

27.

Wu J. Wen Bing Tiao Bian. Beijing: Chinese Press of Traditional Chinese Medicine; 2006.

28.

Hao Y, Li J, Wu Y, Wu J, Lu G, Huang Q. Influences of Xijiao Dihuang decoction combined with Yinqiao powder on virus titre and pathological changes of lung tissue in mice with influenza viral pneumonia. J Beijing Univ Chin Med. 2010;33(11):739–44.

29.

Dong Y, Wu J, Chen D, Li G, Ge D, Qiu Z, Hao Y. Comparing truncated and routine methods in the treatment of mice pneumonia induced by influenza virus. J Beijing Univ Tradit Chin Med. 2015;38(6):388–92.

30.

Chen D, Dong Y, Ren R, You L, Wu J, Hao Y. The comparative study of inhibitory effects of truncated therapy and conventional therapy on lung tissue inflammation of mice with pneumonia induced by influenza virus. J Beijing Univ Tradit Chin Med. 2016;39(5):367–71.

31.

Zhang CY, Zhang S, Wu Y, Jin YZ, Li MG, Wang Q, Hao Y. Effects of Xijiao Dihuang and Yinqiao san decoction on ICAM-1 and VCAM-1 expression in mouse lung tissues and rat pulmonary microvascular endothelial cells infected with influenza virus. Chin J Pathophysiol. 2013;29(09):1685–90.

32.

Zhao Q, Xi R, Zhang SJ, Qi XY, Chen XM, Zhang JJ, Zheng JC, Zhu MY, Li CH, Wu Y. Impacts of the combined medication of Xijiao Dihuang Tang and Yinqiao san on GRK-βAR-Gsα signaling pathways in the lung tissues of mice with influenza viral pneumonia. World J Integrated Tradit Western Med. 2018;13(04):487–91.

33.

Wu Y, Jin Y, Meng J, Wu J, Yu X, Hao Y. Study on effects of serum containing Xijiao Dihuang and Yinqiaosan decoction on inflammatory substances in alveolar macrophages against influenza virus infection. J Tradit Chin Med. 2010;25(12):1974–8.

34.

Zinan X, Wu Y, Zhang C, Shujing Z, Xiangyang C, Shuyu L, Hao Y, Qian W, Xudan W, Zhang S. Xijiao Dihuang decoction combined with Yinqiao powder reverses influenza virusinduced F-actin reorganization in PMVECs by inhibiting ERM phosphorylation. J Tradit Chin Med Sci. 2016;3(1):50–8.

35.

Cheung MC, Spalding PB, Gutierrez JC, Balkan W, Namias N, Koniaris LG, Zimmers TA. Body surface area prediction in normal, hypermuscular, and obese mice. J Surg Res. 2009;153(2):326–31.PubMedCrossRef

36.

Ren Y, Chen X, Li P, Zhang H, Su C, Zeng Z, Wu Y, Xie X, Wang Q, Han J, et al. Si-Miao-Yong-An decoction ameliorates cardiac function through restoring the equilibrium of SOD and NOX2 in heart failure mice. Pharmacol Res. 2019;146:104318.PubMedCrossRef

37.

Bao Y, Gao Y, Jin Y, Cong W, Pan X, Cui X. MicroRNA expression profiles and networks in mouse lung infected with H1N1 influenza virus. Mol Gen Genomics. 2015;290(5):1885–97.CrossRef

38.

Brogaard L, Heegaard PM, Larsen LE, Mortensen S, Schlegel M, Durrwald R, Skovgaard K. Late regulation of immune genes and microRNAs in circulating leukocytes in a pig model of influenza a (H1N2) infection. Sci Rep. 2016;6:21812.PubMedPubMedCentralCrossRef

39.

Brogaard L, Larsen LE, Heegaard P, Anthon C, Gorodkin J, Durrwald R, Skovgaard K. IFN-lambda and microRNAs are important modulators of the pulmonary innate immune response against influenza a (H1N2) infection in pigs. PLoS One. 2018;13(4):e194765.CrossRef

40.

Peng X, Gralinski L, Ferris MT, Frieman MB, Thomas MJ, Proll S, Korth MJ, Tisoncik JR, Heise M, Luo S, et al. Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection. MBIO. 2011;2(6):e00198–11.

41.

Preusse M, Schughart K, Pessler F. Host genetic background strongly affects pulmonary microRNA expression before and during influenza a virus infection. Front Immunol. 2017;8:246.PubMedPubMedCentralCrossRef

42.

Skovgaard K, Cirera S, Vasby D, Podolska A, Breum SO, Durrwald R, Schlegel M, Heegaard PM. Expression of innate immune genes, proteins and microRNAs in lung tissue of pigs infected experimentally with influenza virus (H1N2). Innate Immun. 2013;19(5):531–44.PubMedCrossRef

43.

Tan KS, Choi H, Jiang X, Yin L, Seet JE, Patzel V, Engelward BP, Chow VT. Micro-RNAs in regenerating lungs: an integrative systems biology analysis of murine influenza pneumonia. BMC Genomics. 2014;15:587.PubMedPubMedCentralCrossRef

44.

Liu J, Pei T, Mu J, Zheng C, Chen X, Huang C, Fu Y, Liang Z, Wang Y. Systems pharmacology uncovers the multiple mechanisms of Xijiao Dihuang decoction for the treatment of viral hemorrhagic fever. Evid Based Complement Alternat Med. 2016;2016:9025036.PubMedPubMedCentral

45.

Li R, Xiao J, Qing X, Xing J, Xia Y, Qi J, Liu X, Zhang S, Sheng X, Zhang X, et al. Sp1 mediates a therapeutic role of MiR-7a/b in angiotensin II-induced cardiac fibrosis via mechanism involving the TGF-beta and MAPKs pathways in cardiac fibroblasts. PLoS One. 2015;10(4):e125513.

46.

Amaral AJ, Andrade J, Foxall RB, Matoso P, Matos AM, Soares RS, Rocha C, Ramos CG, Tendeiro R, Serra-Caetano A, et al. miRNA profiling of human naive CD4 T cells links miR-34c-5p to cell activation and HIV replication. EMBO J. 2017;36(3):346–60.PubMedCrossRef

47.

Wang Y, Brahmakshatriya V, Zhu H, Lupiani B, Reddy SM, Yoon BJ, Gunaratne PH, Kim JH, Chen R, Wang J, et al. Identification of differentially expressed miRNAs in chicken lung and trachea with avian influenza virus infection by a deep sequencing approach. BMC Genomics. 2009;10:512.PubMedPubMedCentralCrossRef

48.

Tomita M. Important roles of cellular MicroRNA miR-155 in Leukemogenesis by human T-cell leukemia virus type 1 infection. ISRN Microbiol. 2012;2012:978607.PubMedPubMedCentralCrossRef

49.

Wu J, Gao F, Xu T, Deng X, Wang C, Yang X, Hu Z, Long Y, He X, Liang G, et al. miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling. Int J Oncol. 2018;52(5):1427–42.

50.

Zhang Y, Liu Y, Zhang H, Wang M, Zhang J. Mmu-miR-351 attenuates the survival of cardiac arterial endothelial cells through targeting STAT3 in the atherosclerotic mice. Biochem Biophys Res Commun. 2015;468(1–2):300–5.PubMedCrossRef

51.

Meng F, Rui Y, Xu L, Wan C, Jiang X, Li G. Aqp1 enhances migration of bone marrow mesenchymal stem cells through regulation of FAK and beta-catenin. Stem Cells Dev. 2014;23(1):66–75.PubMedCrossRef

52.

Zhang H, Qin F, Yang L, He J, Liu X, Shao Y, Guo Z, Zhang M, Li W, Fu L, et al. Combination of AQP1 and beta-catenin expression is an independent prognosis factor in astrocytoma patients. Oncotarget. 2017;8(59):99414–28.PubMedPubMedCentralCrossRef

53.

Zhang J, An Y, Gao J, Han J, Pan X, Pan Y, Tie L, Li X. Aquaporin-1 translocation and degradation mediates the water transportation mechanism of acetazolamide. PLoS One. 2012;7(9):e45976.PubMedPubMedCentralCrossRef

54.

Geng ZK, Li YQ, Cui QH, DU RK, Tian JZ. Exploration of the mechanisms of Ge gen decoction against influenza a virus infection. Chin J Nat Med. 2019;17(9):650–62.PubMedPubMedCentral

55.

Ma Q, Yu Q, Xing X, Liu S, Shi C, Luo J. San Wu Huangqin decoction, a Chinese herbal formula, inhibits influenza a/PR/8/34 (H1N1) virus infection in vitro and in vivo. Viruses. 2018;10(3):117.

56.

Ma YJ, Yang J, Fan XL, Zhao HB, Hu W, Li ZP, Yu GC, Ding XR, Wang JZ, Bo XC, et al. Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza a virus in infected human lung epithelial cells. J Cell Mol Med. 2012;16(10):2539–46.PubMedPubMedCentralCrossRef

57.

Law AH, Tam AH, Lee DC, Lau AS. A role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection. Int J Mol Sci. 2013;14(4):7327–40.PubMedPubMedCentralCrossRef

58.

Wang QW, Su Y, Sheng JT, Gu LM, Zhao Y, Chen XX, Chen C, Li WZ, Li KS, Dai JP. Anti-influenza a virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-kappaB signal pathways. PLoS One. 2018;13(1):e191793.

59.

Kujime K, Hashimoto S, Gon Y, Shimizu K, Horie T. p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase regulate RANTES production by influenza virus-infected human bronchial epithelial cells. J Immunol. 2000;164(6):3222–8.PubMedCrossRef

60.

Agron M, Brekhman V, Morgenstern D, Lotan T. Regulation of AP-1 by MAPK signaling in metal-Stressed Sea anemone. Cell Physiol Biochem. 2017;42(3):952–64.PubMedCrossRef

61.

Le Goffic R, Bouguyon E, Chevalier C, Vidic J, Da CB, Leymarie O, Bourdieu C, Decamps L, Dhorne-Pollet S, Delmas B. Influenza a virus protein PB1-F2 exacerbates IFN-beta expression of human respiratory epithelial cells. J Immunol. 2010;185(8):4812–23.PubMedCrossRef

62.

Ludwig S, Ehrhardt C, Neumeier ER, Kracht M, Rapp UR, Pleschka S. Influenza virus-induced AP-1-dependent gene expression requires activation of the JNK signaling pathway. J Biol Chem. 2001;276(24):10990–8.PubMedCrossRef

63.

Al-Ahdal MN, Murugaiah V, Varghese PM, Abozaid SM, Saba I, Al-Qahtani AA, Pathan AA, Kouser L, Nal B, Kishore U. Entry inhibition and modulation of pro-inflammatory immune response against influenza a virus by a recombinant truncated surfactant protein D. Front Immunol. 2018;9:1586.PubMedPubMedCentralCrossRef

64.

Zhang F, Sun X, Zhu Y, Qin W. Downregulation of miR-146a inhibits influenza a virus replication by enhancing the type I interferon response in vitro and in vivo. Biomed Pharmacother. 2019;111:740–50.PubMedCrossRef

65.

Galani IE, Triantafyllia V, Eleminiadou EE, Koltsida O, Stavropoulos A, Manioudaki M, Thanos D, Doyle SE, Kotenko SV, Thanopoulou K, et al. Interferon-lambda mediates non-redundant front-line antiviral protection against influenza virus infection without compromising host fitness. Immunity. 2017;46(5):875–90.PubMedCrossRef

66.

Fox JM, Crabtree JM, Sage LK, Tompkins SM, Tripp RA. Interferon lambda upregulates IDO1 expression in respiratory epithelial cells after influenza virus infection. J Interf Cytokine Res. 2015;35(7):554–62.CrossRef

67.

Kelly A, Robinson MW, Roche G, Biron CA, O'Farrelly C, Ryan EJ. Immune cell profiling of IFN-lambda response shows pDCs express highest level of IFN-lambdaR1 and are directly responsive via the JAK-STAT pathway. J Interf Cytokine Res. 2016;36(12):671–80.CrossRef

68.

Kulling PM, Olson KC, Hamele CE, Toro MF, Tan SF, Feith DJ, Loughran TJ. Dysregulation of the IFN-gamma-STAT1 signaling pathway in a cell line model of large granular lymphocyte leukemia. PLoS One. 2018;13(2):e193429.CrossRef

69.

Pawliczak R, Logun C, Madara P, Barb J, Suffredini AF, Munson PJ, Danner RL, Shelhamer JH. Influence of IFN-gamma on gene expression in normal human bronchial epithelial cells: modulation of IFN-gamma effects by dexamethasone. Physiol Genomics. 2005;23(1):28–45.PubMedCrossRef

Title: The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus
Authors: Ke Li
Xiaoming Chen
Jing Zhong
Hehe Ye
Shujing Zhang
Dongyu Ge
Xudan Wang
Ying Wu
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Pneumonia
Influenza
Published in: BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-020-03074-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The effects of the Xijiao Dihuang decoction combined with Yinqiao powder on miRNA-mRNA profiles in mice infected with influenza a virus

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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