Division of Genetics and Development, Krembil Research Institute, University Health Network, Toronto, ON M5T 2S8, Canada.
Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cells. 2021 Jul 20;10(7):1838. doi: 10.3390/cells10071838.
Ischemia reperfusion injury (IRI) is associated with a broad array of life-threatening medical conditions including myocardial infarct, cerebral stroke, and organ transplant. Although the pathobiology and clinical manifestations of IRI are well reviewed by previous publications, IRI-related transcriptomic alterations are less studied. This study aimed to reveal a transcriptomic hallmark for IRI by using the RNA-sequencing data provided by several studies on non-human preclinical experimental models. In this regard, we focused on the transcriptional responses of IRI in an acute time-point up to 48 h. We compiled a list of highly reported genes in the current literature that are affected in the context of IRI. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and found many of the up-regulated genes to be involved in cell survival, cell surface signaling, response to oxidative stress, and inflammatory response, while down-regulated genes were predominantly involved in ion transport. Furthermore, by GO analysis, we found that multiple inflammatory and stress response processes were affected after IRI. Tumor necrosis factor alpha (TNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were also highlighted in the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In the last section, we discuss the treatment approaches and their efficacy for IRI by comparing RNA sequencing data from therapeutic interventions with the results of our cross-comparison of differentially expressed genes and pathways across IRI.
缺血再灌注损伤(IRI)与一系列危及生命的医疗状况有关,包括心肌梗死、脑卒中和器官移植。尽管以前的出版物已经很好地综述了 IRI 的病理生物学和临床表现,但对 IRI 相关转录组变化的研究较少。本研究旨在通过使用来自非人类临床前实验模型的几项研究提供的 RNA 测序数据揭示 IRI 的转录组特征。在这方面,我们专注于 IRI 在急性时间点(长达 48 小时)的转录反应。我们编译了一份在 IRI 背景下受影响的当前文献中高度报道的基因列表。我们进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,发现许多上调基因参与细胞存活、细胞表面信号转导、氧化应激反应和炎症反应,而下调基因主要参与离子转运。此外,通过 GO 分析,我们发现 IRI 后多个炎症和应激反应过程受到影响。肿瘤坏死因子-α(TNF)和核因子 kappa-轻链增强子的 B 细胞激活(NF-κB)信号通路也在京都基因与基因组百科全书富集分析中得到了强调。在最后一节中,我们通过比较治疗干预的 RNA 测序数据与我们跨比较 IRI 差异表达基因和途径的结果,讨论了 IRI 的治疗方法及其疗效。