ArticleGut2026
Crosstalk between liver sinusoidal endothelial cells and hepatocytes via IL-1α-IL1R1 axis exacerbates ischaemia/reperfusion injury in aged livers.
Article in Gut, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Gut Microbiota and Ageing: A Critical Crosstalk in Alcohol-Related Liver Disease.Microorganisms · 2026Review
- HSP90AA1 inhibits the Jun/Fos pathway to rescue hepatocytes from cuproptosis during ischemia-reperfusion injury.Clinical and experimental medicine · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles attenuate liver transplantation-induced ischemia/reperfusion injury by suppressing hepatocellular complement C5 expression.Journal of nanobiotechnology · 2026Article
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWith population ageing, elderly patients account for a growing proportion of hepatic surgery recipients. Hepatic ischaemia-reperfusion injury (HIRI) is a major cause of postoperative liver dysfunction, particularly in aged livers, yet its mechanisms remain poorly understood.
objectiveWe aimed to elucidate critical cellular interactions and molecular mechanisms underlying aggravated HIRI in aged livers to uncover therapeutic targets.
designSingle-cell RNA sequencing and spatial transcriptomics were performed on liver tissues from humans, rats and mice across ages to define key cell types and intercellular signalling. HIRI and liver transplantation animal models, primary cell co-cultures and adeno-associated virus-mediated gene knockdown were used to prove cellular function and mechanisms. Neutralising antibody was used to assess therapeutic efficacy.
resultsIntegrated analyses revealed a significant enrichment of senescent liver sinusoidal endothelial cells (LSECs) in aged livers, with the most prominent age-associated increase in crosstalk with hepatocytes, thereby promoting inflammation. Further investigation demonstrated increased transcriptional activity of myeloid ecotropic viral integration site 2 (MEIS2) in senescent LSECs, driving interleukin (IL)-1α expression via promoter binding and the IL-1α-IL1R1 axis subsequently activated NF-κB signalling in hepatocytes, enhancing inflammatory cytokine production. Interestingly, LSECs were also most strongly influenced by hepatocytes during liver ageing, as hepatocyte-derived TNF-α further enhanced MEIS2 transcriptional activity in LSECs, establishing a proinflammatory positive feedback loop. Furthermore, we confirmed that neutralising IL-1α effectively alleviated HIRI in aged livers.
conclusionOur findings identify the crosstalk between LSECs and hepatocytes in aged livers aggravating HIRI via MEIS2/IL-1α/IL1R1/TNF-α axis, suggesting that IL-1α neutralising antibody can be exploited as a promising therapeutic strategy for aged HIRI.
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