Biomolecules
Organ- and Cell-Specific Induction of the NFE2L2 Antioxidant Programme After Human Graft Reperfusion
By Oh H and Ahn SH.
Abstract
Introduction
Reactive oxygen species at reperfusion are held as a shared injury mechanism across organs, so antioxidant strategies are systemic. Whether the graft's own response is uniform is untested in human tissue.
Methods
Eight public cohorts of paired pre/post-reperfusion human transplant biopsies (kidney, 96 pairs; liver, 40; lung, 54) were analysed with a pre-specified 99-gene antioxidant/ROS panel in ten modules. Within-person differences were compared between organs (paired Wilcoxon, Benjamini-Hochberg) and pooled by random-effects meta-analysis. Two single-cell datasets (lung, 117,549 cells, six recipients; liver, 8802 cells, one donor) resolved cell type. All measures are transcriptional.
Results
Antioxidant transcription did not rise as a whole: constitutive scavenging enzyme transcripts fell or were unchanged in every organ. Increase was confined to the NFE2L2-dependent antioxidant programme, graded by organ (lung 98.1%, liver 92.5%, kidney 62.5%; pooled dz 0.99, I2 = 89%), with 72.5% of that heterogeneity attributable to organ and no covariate significant after correction. Single-cell data support involvement of epithelium, endothelium, fibroblasts and resident macrophages, but not recruited myeloid cells.