Abstract
AbstractHepatic 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Beijing Municipality
Beijing Municipal Commission of Education
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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