Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli.

Ruicheng Yang,Wentong Liu,Ling Miao,Xiaopei Yang,Jiyang Fu,Xiangru Wang,Fei Huang,Chen Tan,Bojie Xu,Huanchun Chen,Beibei Dou

doi:10.1038/srep38903

Ruicheng Yang, Wentong Liu + Show 9 more

Open Access

https://doi.org/10.1038/srep38903

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Journal: Scientific Reports	Publication Date: Dec 1, 2016
Citations: 42	License type: CC BY 4.0

Affiliation: Huazhong Agricultural University

Abstract

Accumulating studies have indicated the influence of long non-coding RNAs (lncRNAs) on various biological processes as well as disease development and progression. However, the lncRNAs involved in bacterial meningitis and their regulatory effects are largely unknown. By RNA-sequencing, the transcriptional profiles of host lncRNAs in primary human brain microvascular endothelial cells (hBMECs) in response to meningitic Escherichia coli were demonstrated. Here, 25,257 lncRNAs were identified, including 24,645 annotated lncRNAs and 612 newly found ones. A total of 895 lncRNAs exhibited significant differences upon infection, among which 382 were upregulated and 513 were downregulated (≥2-fold, p < 0.05). Via bioinformatic analysis, the features of these lncRNAs, their possible functions, and the potential regulatory relationships between lncRNAs and mRNAs were predicted. Moreover, we compared the transcriptional specificity of these differential lncRNAs among hBMECs, human astrocyte cell U251, and human umbilical vein endothelial cells, and demonstrated the novel regulatory effects of proinflammatory cytokines on these differential lncRNAs. To our knowledge, this is the first time the transcriptional profiles of host lncRNAs involved in E. coli-induced meningitis have been reported, which shall provide novel insight into the regulatory mechanisms behind bacterial meningitis involving lncRNAs, and contribute to better prevention and therapy of CNS infection.

Highlights

Inflammatory storm and central nervous system (CNS) dysfunction[16]
We identified only two long non-coding RNAs (lncRNAs) in U251 cells, lnc-ITGA11-1 and lnc-DIRC1-1, for which the levels were not affected by meningitic E. coli infection, while the remaining ones exhibited similar decreases in hBMECs, U251 cells and HUVECs (Fig. 7B and D)
The aim of this study is to explore the potential key host lncRNAs that are involved in bacterial meningitis

Summary

Introduction

Inflammatory storm and CNS dysfunction[16]. there is a need to reveal the mechanism underlying the penetration of the BBB by CNS-infecting bacteria, especially regarding how they interact with the host BBB and regulate host targets, thereby contributing to infection. Numerous studies have reported CNS-infecting bacterial invasion of the BBB, the receptors on BMECs with which these bacteria interact, the regulation of host molecules that mediate BBB disruption, as well as characterisation of microRNAs that regulate tight junction expression[17]. To fully elucidate the interaction between CNS-infecting bacteria and the host BBB, as well as the regulatory mechanisms involved in this, in the current study, we applied RNA-seq and bioinformatic approaches to identify potential host lncRNAs active in primary hBMECs in response to the infection of meningitic E. coli strain PCN033, a brain isolate that has been demonstrated to disrupt the BBB as well as inducing CNS inflammatory responses[28]. These observations together suggest the novel concept that lncRNAs are involved in bacterial meningitis, which should provide more regulatory host targets and contribute to further study on the pathogenic mechanisms involved in this disease, as well as better prevention and therapy for it

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