Microarray profiling of lung long non-coding RNAs and mRNAs in lipopolysaccharide-induced acute lung injury mouse model.

Juan Wang,Kai Liu,Da-Jiang Li,Zhen-Ni Chen,Hao Wang,Yong-Chun Shen,Zhi-Cheng Yuan,Fu-Qiang Wen

doi:10.1042/bsr20181634

Juan Wang, Kai Liu + Show 6 more

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https://doi.org/10.1042/bsr20181634

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Journal: Bioscience reports	Publication Date: Apr 30, 2019
Citations: 17	License type: CC BY 4.0

Affiliation: West China Hospital of Sichuan University

Abstract

Long non-coding RNAs (lncRNAs) are involved in various biological processes as well as many respiratory diseases, while the role of lncRNAs in acute lung injury (ALI) remains unclear. The present study aimed to profile the expression of lung lncRNAs and mRNAs in lipopolysaccharide (LPS)-induced ALI mouse model. C57BL/6 mice were exposed to LPS or phosphate-buffered saline for 24 h, and lncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Bioinformatics analysis gene ontology including (GO) and pathway analysis and cell study in vitro was used to investigate potential mechanisms. Based on the microarray results, 2632 lncRNAs and 2352 mRNAs were differentially expressed between ALI and control mice. The microarray results were confirmed by the quantitative real-time PCR (qRT-PCR) results of ten randomized selected lncRNAs. GO analysis showed that the altered mRNAs were mainly related to the processes of immune system, immune response and defense response. Pathway analysis suggests that tumor necrosis factor (TNF) signaling pathway, NOD-like receptor pathway, and cytokine–cytokine receptor interaction may be involved in ALI. LncRNA-mRNA co-expression network analysis indicated that one individual lncRNA may interact with several mRNAs, and one individual mRNA may also interact with several lncRNAs. Small interfering RNA (siRNA) for ENSMUST00000170214.1, - ENSMUST00000016031.13 significantly inhibited LPS-induced TNF-α and interleukin (IL)-1β production in murine RAW264.7 macrophages. Our results found significant changes of lncRNAs and mRNAs in the lungs of LPS-induced ALI mouse model, and intervention targeting lncRNAs may attenuate LPS-induced inflammation, which may help to elucidate the role of lncRNAs in the pathogenesis and treatment of ALI.

Highlights

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a sequence of lung injuries arising from a wide variety of stimulus, followed by uncontrolled inflammation, which frequently result in multiple organ dysfunction with high mortality [1]
Hematoxylin and Eosin (HE)-staining showed that LPS dramatically increased the leukocyte-infiltration in mouse lungs (Figure 1A,B), ALI score increased significantly in LPS-challenged mice (P
Recent study reported that long non-coding RNA (lncRNA)-HOTAIR increase the release of tumor necrosis factor (TNF)-α in the cardiomyocytes of LPS-induced sepsis mice by activating NF-κB through the phosphorylation of NF-κB p65 subunit, suggesting that lncRNA may plays a role in ALI through the regulation of TNF-α [22]

Summary

Introduction

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are a sequence of lung injuries arising from a wide variety of stimulus, followed by uncontrolled inflammation, which frequently result in multiple organ dysfunction with high mortality [1]. Our previous study observed significant changes of lncRNAs expression profiles in cigarette-smoke exposed mouse lung and revealed a potential role of lncRNAs in the pathogenesis of cigarette smoke-associated airway inflammatory disorders [11].

Results

Conclusion