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Changes of energy metabolism-related proteins before and after donor liver transplantation in patients with ischemia-reperfusion injury

ABSTRACT: To investigate the molecular mechanisms underlying ischemia-reperfusion (IR) injury in liver transplantation, RNA sequencing (RNA-seq) was performed on liver specimens obtained at various stages: before ischemia and post-reperfusion. The RNA-seq analysis aimed to profile gene expression changes in response to IR injury and identify key molecular pathways involved in liver dysfunction, with a particular focus on energy metabolism-related proteins PPARα. This approach provides a comprehensive understanding of the transcriptional alterations that occur during liver transplantation, highlighting the changes in metabolic pathways such as gluconeogenesis and fatty acid oxidation. These findings may offer insights into therapeutic strategies for mitigating IR-induced damage and enhancing liver transplantation outcomes by targeting energy metabolism pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE283907 | GEO | 2025/01/23

REPOSITORIES: GEO

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Project description:INTRODUCTION Ischemia and reperfusion injury (IRI)-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest 1. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery 1. IRI, one of the biggest challenges for organ transplantation, continues to be a vital source of morbidity among recipients, especially in liver transplantation 2. With the enlarging shortage of available donor livers, the increased use of extended criteria donor grafts further increases IRI, adversely affecting both short-term and long-term outcomes of graft and patient survival 3. Numerous studies have investigated the benefits of pharmacological, heat shock, and ischemic preconditioning interventions aimed at decreasing liver IRI 4. However, the benefit was limited. Our center has been making great effort in conquering IRI and have developed a novel surgical technique called ischemia-free liver transplantation 5. It is an ultimate method to overcome IRI in liver transplantation, but there is still a long way to popularize it. As a result, it is still of great significance to study IRI and identify the core genes in the process and the underlying mechanism. Comprehensive bioinformatics analysis has been increasingly important as a method to study various pathological and physiological condition 6. By enrolling multiple omics or combining different types of omics, comprehensive bioinformatics analysis was able to recognize key factors that could have potentially pathogenic impact such as gene expression, protein function, and downstream pathways. With the rapid development of high-throughput sequencing technologies, several transcriptomic datasets on IRI of liver transplantation have become available in the Gene Expression Omnibus (GEO) database. Herein, we recruited 3 GEO datasets to conduct comprehensive analysis with the GEO dataset from our center. Moreover, we performed the first proteome of liver tissues to study liver IRI. Then the transcriptome and proteome were used for combined analysis to reveal key factors in liver IRI.

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Changes of energy metabolism-related proteins before and after donor liver transplantation in patients with ischemia-reperfusion injury

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