Transcriptomic Hallmarks of Ischemia-Reperfusion Injury

Cells. 2021 Jul 20;10(7):1838. doi: 10.3390/cells10071838.

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.

Keywords: RNA-seq; ischemia reperfusion injury; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Agents / therapeutic use
  • Cell- and Tissue-Based Therapy / methods
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks / drug effects
  • Humans
  • Ischemic Postconditioning / methods
  • Ischemic Preconditioning / methods
  • Kidney / blood supply
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Liver / blood supply
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Metabolic Networks and Pathways / drug effects
  • Metabolic Networks and Pathways / genetics*
  • Mice
  • Molecular Sequence Annotation
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Rats
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / therapy
  • Sequence Analysis, RNA
  • Signal Transduction
  • Spinal Cord / blood supply
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Transcriptome*
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cardiovascular Agents
  • NF-kappa B
  • Tumor Necrosis Factor-alpha