Transcriptomic Hallmarks of Ischemia-Reperfusion Injury

Abstract

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.

IKK1 aggravates ischemia–reperfusion kidney injury by promoting the differentiation of effector T cells

“…The activation of NFκB plays a pivotal role in renal injury after IRI as we and others have shown previously [ 9 , 15 , 30 ]. NFκB is activated both in renal parenchymal and in infiltrating inflammatory cells after IRI-induction [ 31 – 35 ]. Therefore, in the current experiments using RNA sequencing analysis we now confirmed that (1) NFκB pathway is activated up to 28d after induction of IRI (Fig.…”

Signaling Pathways Involved in Myocardial Ischemia–Reperfusion Injury and Cardioprotection: A Systematic Review of Transcriptomic Studies in Sus scrofa

“…Meanwhile, in the BZ, signaling pathways associated with inflammation, hypoxia, and angiogenesis that become upregulated soon after reperfusion remain present at chronic phases, even when ECM remodeling and myogenesis processes prevail. Many of the pathways upregulated after IRI have been previously described in other non-human, preclinical experimental models [ 20 ]. However, a direct comparison of the transcriptomic regulation of myocardial IRI between the pig and other animal models has not been addressed, and further studies are needed to uncover any distinct differences between animal models.…”

“…Studying gene expression datasets derived from microarrays and high-throughput sequencing can reveal novel functional interdependencies among signaling pathways that concertedly determine cellular responses [ 18 , 19 ]. Understanding the timing of transcriptional events and their modulation by cardioprotective strategies is critical to address the pathophysiology of myocardial IRI [ 20 ]. Despite the relevance of pigs for translational studies of AMI, only a few studies have identified the transcriptomic landscape of myocardial IRI and how changes in gene expression shape cellular signaling pathways in response to injury.…”

Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia‐reperfusion in rats

“…Cerebral ischemia-reperfusion injury is divided into complete ischemia-reperfusion injury and incomplete ischemia-reperfusion injury according to the degree of ischemia. 1 Incomplete cerebral ischemia-reperfusion injury is mostly seen in hemorrhagic shock caused by trauma, surgery, or other certain diseases. 2 The mechanisms of cerebral ischemia-reperfusion injury are not fully understood.…”