Integrated analysis of dysregulated microRNA and mRNA expression in intestinal epithelial cells following ethanol intoxication and burn injury.
Integrated analysis of dysregulated microRNA and mRNA expression in intestinal epithelial cells following ethanol intoxication and burn injury.
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DOI：
10.1038/s41598-021-99281-1
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发表时间：
2021-10-12
影响因子：
4.6
通讯作者：
Choudhry MA
中科院分区：
文献类型：
--
作者：
Herrnreiter CJ;Li X;Luck ME;Zilliox MJ;Choudhry MA
肠屏障功能障碍通常与酒精中毒和烧伤后的病理学有关。微小RNA（miRNAs）是基因表达的负调控因子，在肠道内稳态中发挥核心作用，尽管其在酒精和烧伤后的作用知之甚少。我们对miRNA和RNA测序数据进行了综合分析，以确定小肠上皮细胞（IEC）内的相互作用网络，这些相互作用可以促进肠道屏障破坏。小鼠灌胃约2.9 g/kg乙醇，4小时后给予约12.5% TBSA全层烫伤。一天后，收获IEC，并提取总RNA用于RNA-seq和miRNA-seq 13 RNA测序显示在酒精和烧伤后的IEC中有712个差异表达基因（DEG）（padj < 0.05）。此外，miRNA测序显示了17个差异表达的miRNA（DEM）（padj < 0.1）。利用miRNet，miRDB和TargetScan数据库，我们确定了验证和预测的miRNA基因靶标。小RNA测序数据与mRNA测序结果的整合鉴定了miRNA和靶表达的相关变化。上调的miRNA与增殖（miR-98- 3 p和miR-381- 3 p）和细胞粘附（miR-29 a-3 p、miR-429- 3 p和miR 3535）的降低相关，而下调的miRNA与凋亡（Let-7 d-5 p和miR-130 b-5 p）和代谢（miR-674- 3 p和miR-185- 5 p）的上调相关。总的来说，这些研究结果表明，酒精和烧伤显著改变了IEC的mRNA和miRNA表达谱，并揭示了许多miRNA-mRNA相互作用，这些相互作用调节酒精和烧伤后肠道屏障功能的关键途径。
Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj < 0.05) in IECs following alcohol and burn injury. Furthermore, miRNA sequencing revealed 17 differentially expressed miRNAs (DEMs) (padj < 0.1). Utilizing the miRNet, miRDB and TargetScan databases, we identified both validated and predicted miRNA gene targets. Integration of small RNA sequencing data with mRNA sequencing results identified correlated changes in miRNA and target expression. Upregulated miRNAs were associated with decreased proliferation (miR-98-3p and miR-381-3p) and cellular adhesion (miR-29a-3p, miR-429-3p and miR3535), while downregulated miRNAs were connected to upregulation of apoptosis (Let-7d-5p and miR-130b-5p) and metabolism (miR-674-3p and miR-185-5p). Overall, these findings suggest that alcohol and burn injury significantly alters the mRNA and miRNA expression profile of IECs and reveals numerous miRNA–mRNA interactions that regulate critical pathways for gut barrier function after alcohol and burn injury.
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DOI：
10.1097/shk.0000000000000900
发表时间：
2017-12
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Hammer AM;Morris NL;Cannon AR;Khan OM;Gagnon RC;Movtchan NV;van Langeveld I;Li X;Gao B;Choudhry MA
通讯作者：
Choudhry MA
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.7
作者：
Belen Ruiz-Roso, Maria;Gil-Zamorano, Judit;Davalos, Alberto
通讯作者：
Davalos, Alberto
影响因子：
2.1
作者：
Hadjizacharia, P.;O'Keeffe, T.;Plurad, D. S.;Green, D. J.;Brown, C. V. R.;Chan, L. S.;Demetriades, D.;Rhee, P.
通讯作者：
Rhee, P.
影响因子：
14.9
作者：
Chang, Le;Zhou, Guangyan;Xia, Jianguo
通讯作者：
Xia, Jianguo