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通过RNA测序数据和GEO数据集的综合分析,鉴定与脂多糖诱导的急性肺损伤发病及虾青素治疗效果相关的稳健基因特征。

Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets.

作者信息

Mao Kaimin, Geng Wei, Liao Yuhan, Luo Ping, Zhong Hua, Ma Pei, Xu Juanjuan, Zhang Shuai, Tan Qi, Jin Yang

机构信息

Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

Center for Translational Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.

出版信息

Aging (Albany NY). 2020 Sep 23;12(18):18716-18740. doi: 10.18632/aging.104042.

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions predominantly arising from uncontrolled inflammatory reactions. It has been found that the administration of astaxanthin (AST) can exert protective effects against lipopolysaccharide (LPS)-induced ALI; however, the robust genetic signatures underlying LPS induction and AST treatment remain obscure. Here we performed a statistical meta-analysis of five publicly available gene expression datasets from LPS-induced ALI mouse models, conducted RNA-sequencing (RNA-seq) to screen differentially expressed genes (DEGs) in response to LPS administration and AST treatment, and integrative analysis to determine robust genetic signatures associated with LPS-induced ALI onset and AST administration. Both the meta-analyses and our experimental data identified a total of 198 DEGs in response to LPS administration, and 11 core DEGs ( and ) were identified to be associated with AST therapeutic effects. Further, the 11 core DEGs were verified by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and functional enrichment analysis revealed that these genes are primarily associated with neutrophils and chemokines. Collectively, these findings unearthed the robust genetic signatures underlying LPS administration and the molecular targets of AST for ameliorating ALI/ARDS which provide directions for further research.

摘要

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是主要由失控的炎症反应引起的危及生命的临床病症。已发现虾青素(AST)的给药可对脂多糖(LPS)诱导的ALI发挥保护作用;然而,LPS诱导和AST治疗背后强大的基因特征仍不清楚。在此,我们对来自LPS诱导的ALI小鼠模型的五个公开可用基因表达数据集进行了统计荟萃分析,进行了RNA测序(RNA-seq)以筛选响应LPS给药和AST治疗的差异表达基因(DEG),并进行综合分析以确定与LPS诱导的ALI发病和AST给药相关的强大基因特征。荟萃分析和我们的实验数据均确定了总共198个响应LPS给药的DEG,并且鉴定出11个核心DEG(以及)与AST治疗效果相关。此外,通过定量实时PCR(qRT-PCR)和免疫组织化学(IHC)验证了这11个核心DEG,功能富集分析表明这些基因主要与中性粒细胞和趋化因子相关。总的来说,这些发现揭示了LPS给药背后强大的基因特征以及AST改善ALI/ARDS的分子靶点,为进一步研究提供了方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a4/7585091/89650bd5a9b3/aging-12-104042-g001.jpg

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