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Full Length Article | Open Access

Multi-time point transcriptomics and metabolomics reveal key transcription and metabolic features of hepatic ischemia-reperfusion injury in mice

Qi Lia,1, Xiaoyan Qina,b,1, Liangxu Wanga, Dingheng Hua, Rui Liaoa, Huarong Yuc( ), Zhongjun Wua( ), Yanyao Liua( )
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
Department of General Surgery and Trauma Surgery, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China
Research Center of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China

1 These authors have contributed equally to this work and share first authorship.

Peer review under the responsibility of the Genes & Diseases Editorial Office, in alliance with the Association of Chinese Americans in Cancer Research (ACACR, Baltimore, MD, USA).

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Abstract

Hepatic ischemia-reperfusion injury is an unavoidable surgical complication of liver transplantation and the leading cause of poor graft function and increased mortality post-transplantation. Multiple mechanisms have been implicated in ischemia-reperfusion injury; however, the characteristic changes at the transcriptional and metabolic levels in the early, intermediate, and late phases of ischemia-reperfusion injury remain unclear. In the study, mice underwent laparotomy following anesthesia, and the blood vessels of the liver were clipped using a vascular clamp to form 70% warm ischemia of the liver. Mouse liver sections and serum samples were collected and divided into the Sham, I1R12, I1R24, and I1R48 groups. Transcriptomics and metabolomics analyses were performed to study characteristic alterations during the early, intermediate, and late phases of ischemia-reperfusion injury. Quantitative real-time PCR was used to validate the critical differentially expressed genes. The differentially expressed genes and metabolites were identified by transcriptomics and metabolomics analyses. Moreover, GO and KEGG enrichment analyses indicated that glucose metabolism remodeling, inflammatory response activation, and lipid metabolism remodeling were characteristic changes in the early, intermediate, and late phases of ischemia-reperfusion injury, respectively. In summary, our study revealed the importance of glucolipid metabolism in ischemia-reperfusion injury and provided potential therapeutic intervention targets and a new perspective to explore the underlying mechanisms of ischemia-reperfusion injury.

Keywords

InflammationLiver ischemia-reperfusion injuryMetabolic remodelingMetabolomicsTranscriptomics

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Genes & Diseases
Volume 12 Issue 2,
March 2025
Article number: 101465
DOI: 10.1016/j.gendis.2024.101465
Cite this article:
Li Q, Qin X, Wang L, et al. Multi-time point transcriptomics and metabolomics reveal key transcription and metabolic features of hepatic ischemia-reperfusion injury in mice. Genes & Diseases, 2025, 12(2): 101465. https://doi.org/10.1016/j.gendis.2024.101465

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Received: 09 January 2024
Revised: 03 October 2024
Accepted: 02 November 2024
Published: 17 November 2024
© 2024 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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