Intestinal mRNA expression profile and bioinformatics analysis in a methamphetamine-induced mouse model of inflammatory bowel disease.
Intestinal mRNA expression profile and bioinformatics analysis in a methamphetamine-induced mouse model of inflammatory bowel disease.
复制标题
甲基苯丙胺诱导的炎症性肠病小鼠模型肠道 mRNA 表达谱和生物信息学分析
DOI：
10.21037/atm-20-7741
复制
发表时间：
2020-12
影响因子：
--
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Sun J;Chen F;Chen C;Zhang Z;Zhang Z;Tian W;Yu J;Wang K
背景甲基苯丙胺的使用已经成为一个严重的全球公共卫生问题，并给医疗服务带来了越来越大的负担。使用甲基苯丙胺引起的腹部并发症并不常见，常常被临床医生忽视。与使用甲基苯丙胺相关的确切的肠道病理改变和转录反应尚不清楚。这项研究试图使用下一代RNA测序来研究甲基苯丙胺诱导的炎症性肠病(IBD)小鼠模型中的转录组。方法取甲基苯丙胺组(n=5)和对照组(n=5)回肠组织，进行RNA测序。然后进行生物信息学和组织病理学分析。分析肠道组织样本的表达谱，整合其表达谱以获得差异表达基因，并利用生物信息学进行分析。基因本体论和京都百科全书对差异表达基因进行了路径富集化分析。结果共鉴定出差异表达基因326个，其中上调基因120个，下调基因206个。基因本体论分析表明，差异表达基因的生物学过程主要集中在细胞分解代谢过程、内吞作用和自噬的调节上。主要细胞成分包括内质和内吞泡泡、细胞骨架、黏附连接、局灶粘连、胞体和溶酶体。分子功能包括蛋白转移酶、GTP酶和蛋白水解酶活性、肌动蛋白结合和蛋白质-脂质复合体结合。京都百科全书的基因和基因组路径分析表明，差异表达的基因主要涉及细菌对上皮细胞的入侵、内质网中的蛋白质加工、肌动蛋白细胞骨架的调节以及T细胞受体信号通路。在IBD和甲基苯丙胺处理的肠道组织之间发现了一组重叠的基因。结论本研究首次使用高通量RNA测序技术对甲基苯丙胺处理小鼠的肠道样本进行了分析。这项研究揭示了可能参与一种特殊类型的甲基苯丙胺诱导的IBD发病机制的关键分子。这些结果为甲基苯丙胺滥用和IBD之间的关系提供了新的见解。
Background Methamphetamine use has become a serious global public health problem and puts increasing burdens on healthcare services. Abdominal complications caused by methamphetamine use are uncommon and often go ignored by clinicians. The exact intestinal pathological alterations and transcriptomic responses associated with methamphetamine use are not well understood. This study sought to investigate the transcriptome in a methamphetamine-induced mouse model of inflammatory bowel disease (IBD) using next-generation RNA sequencing. Methods Tissues from the ileum of methamphetamine-treated mice (n=5) and control mice (n=5) were dissected, processed and applied to RNA-sequencing. Bioinformatics and histopathological analysis were then performed. The expression profiles of intestinal tissue samples were analyzed and their expression profiles were integrated to obtain the differentially expressed genes and analyzed using bioinformatics. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the differentially expressed genes were performed using Metascape. Results A total of 326 differentially expressed genes were identified; of these genes, 120 were upregulated and 206 were downregulated. The Gene Ontology analysis showed that the biological processes of the differentially expressed genes were focused primarily on the regulation of cellular catabolic processes, endocytosis, and autophagy. The main cellular components included the endoplasmic and endocytic vesicles, cytoskeleton, adherens junctions, focal adhesions, cell body, and lysosomes. Molecular functions included protein transferase, GTPase and proteinase activities, actin-binding, and protein-lipid complex binding. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the differentially expressed genes were mainly involved in bacterial invasion of epithelial cells, protein processing in the endoplasmic reticulum, regulation of the actin cytoskeleton, and T-cell receptor signaling pathways. A set of overlapping genes between IBD and methamphetamine-treated intestinal tissues was discovered. Conclusions The present study is the first to analyze intestinal samples from methamphetamine-treated mice using high-throughput RNA sequencing. This study revealed key molecules that might be involved in the pathogenesis of a special type of methamphetamine-induced IBD. These results offer new insights into the relationship between methamphetamine abuse and IBD.
登录
查看更多内容
影响因子：
48
作者：
Li T;Wernersson R;Hansen RB;Horn H;Mercer J;Slodkowicz G;Workman CT;Rigina O;Rapacki K;Stærfeldt HH;Brunak S;Jensen TS;Lage K
通讯作者：
Lage K
DOI：
10.1186/1471-2210-6-6
发表时间：
2006-03-03
期刊：
BMC pharmacology
影响因子：
--
作者：
Han DD;Gu HH
通讯作者：
Gu HH
影响因子：
3.6
作者：
Jilling, T;Lu, J;Caplan, MS
通讯作者：
Caplan, MS
影响因子：
15.9
作者：
Meriwether, David;Sulaiman, Dawoud;Reddy, Srinivasa T.
通讯作者：
Reddy, Srinivasa T.
影响因子：
--
作者：
Dörfel MJ;Huber O
通讯作者：
Huber O