Candidate Genes as Biomarkers in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome Based on mRNA Expression Profile by Next-Generation RNA-Seq Analysis.

Qi-Quan Wan,Di Wu,Qi-Fa Ye

doi:10.1155/2018/4384797

Abstract

Up until now, the regulation mechanism at the level of gene during lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) remains unclear. The discovery of differentially expressed genes (DEGs) between LPS-induced ARDS rats and normal rats by next-generation RNA sequencing analysis is of particular interest for the current study. These DEGs may help clinical diagnosis of ARDS and facilitate the selection of the optimal treatment strategy. Randomly, 20 rats were equally divided into 2 groups, the control group and the LPS group. Three rats from each group were selected at random for RNA sequencing analysis. Sequence reads were obtained from Illumina HiSeq4000 and mapped onto the rat reference genome RN6 using Hisat2. We identified 5244 DEGs (Fold_Change > 1.5, and P < 0.05) in the lung tissues from LPS-treated rats compared with normal rats, including 1413 upregulated and 3831 downregulated expressed genes. Lots of chemokine family members were among the most upregulated genes in LPS group. Gene ontology (GO) analysis revealed that almost all of the most enriched and meaningful biological process terms were mainly involved in the functions like immune-inflammation response and the pathways like cytokine-cytokine receptor interaction. We also found that, as for GO molecular function terms, the enriched terms were mainly related to chemokines and cytokines. DEGs with fold change over 100 were verified by quantitative real-time polymerase chain reaction and reanalyzed by gene-gene coexpression network, and the results elucidated central roles of chemokines in LPS-induced ARDS. Our results revealed some new biomarkers for uncovering mechanisms and processes of ARDS.

Highlights

The acute respiratory distress syndrome (ARDS) is a lifethreatening diffuse lung disease owing to direct or indirect lung injury factors, such as pneumonia, severe sepsis, aspiration, drug toxicity, and multiple blood transfusion [1]
Almost all of the most enriched and meaningful biological process (BP) terms were related to immune-inflammation response, for instance, “Fc-gamma receptor signaling pathway (GO:0038094),” “response to interferon-beta (GO:0035456),” “cellular response to interferon-beta (GO:0035458),” “Toll-like receptor 2 signaling pathway (GO:00034134),” “immune response (GO:0006955),” “immune response process (GO:0002376),” “response to other organism (GO:0051707),” and “innate immune response (GO:0045087).”
Using RNA sequencing (RNA-Seq) analysis, we identified 5244 differentially expressed genes (DEGs) in the lung tissues from LPS-treated rats compared with normal rats

Summary

Introduction

The acute respiratory distress syndrome (ARDS) is a lifethreatening diffuse lung disease owing to direct or indirect lung injury factors, such as pneumonia, severe sepsis, aspiration, drug toxicity, and multiple blood transfusion [1]. It is characterized by an excessive lung inflammatory response, which can lead to the increased alveolar-capillary permeability, diffused pulmonary interstitial and alveolar edema, and impaired gas exchange functions and reduced alveolar fluid clearance of the lungs with consequent hypoxemia [1,2,3]. Some genes were demonstrated to be associated with ARDS, currently little is known regarding the regulation mechanism at the level of gene, leading to the lack of an effective therapeutic method for severe cases [12,13,14,15]

Results

Discussion

Conclusion