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

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

doi:10.1186/s12906-020-03074-4

Abstract

BackgroundMicroRNAs (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.MethodsWe 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.ResultsThe 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.ConclusionsMiRNAs 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.

Highlights

MicroRNAs play vital roles in acute inflammatory and antiviral responses during influenza A virus (IAV) infection
Xijiao Dihuang decoction combined with Yinqiao powder (XDY) is a classical compound prescription of traditional Chinese medicine derived from Wenbing Tiaobian, which was first created by Wu, Jutong in the Qing Dynasty
Amelioration of clinical manifestations and pathological alterations by XDY in FM1-infected mice We validated the therapeutic effect of XDY on FM1induced pneumonia by observing the clinical manifestations and detecting lung histopathologic changes

Summary

Introduction

MicroRNAs (miRNAs) play vital roles in acute inflammatory and antiviral responses during influenza A virus (IAV) infection. 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. By activating innate and adaptive immunity, IAV triggers acute inflammatory responses, including widespread epithelial damage, multifocal destruction, desquamation of the trachea, vascular leakage and lung oedema [1,2,3]. These inflammatory responses are associated with the expression of immune response-related genes [4]. Wu et al reported that the TGF-β pathway might be involved in the pathophysiological process underlying A/ PuertoRico/8/34 (H1N1) (PR8) and A/Beijing/501/2009 (H1N1) (BJ501) infection and was activated via the upregulation of miR-223 and miR-155 in the lungs of mouse models [10]

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