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Spatial transcriptomics analysis of zone-dependent hepatic ischemia-reperfusion injury murine model
Hepatic ischemia-reperfusion (I/R) injury is a common complication in liver transplantation. The connection between I/R-induced injury response and liver heterogeneity has yet to be fully understood. In this study, we converge histopathological examination with spatial transcriptomics to dissect I/R...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938905/ https://www.ncbi.nlm.nih.gov/pubmed/36804628 http://dx.doi.org/10.1038/s42003-023-04564-0 |
Sumario: | Hepatic ischemia-reperfusion (I/R) injury is a common complication in liver transplantation. The connection between I/R-induced injury response and liver heterogeneity has yet to be fully understood. In this study, we converge histopathological examination with spatial transcriptomics to dissect I/R injury patterns and their associated molecular changes, which reveal that the pericentral zones are most sensitive to I/R injury in terms of histology, transcriptomic changes, and cell type dynamics. Bioinformatic analysis of I/R injury-related pathways predicts that celastrol can protect against liver I/R injury by inducing ischemic pre-conditioning, which is experimentally validated. Mechanistically, celastrol likely implements its protective effect against I/R injury by activating HIF1α signaling and represents a potential strategy for resolving liver I/R. |
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