The spatially resolved kidney transcriptome signatures in rat models of trauma-induced acute kidney injury

To elucidate the molecular mechanisms underlying trauma-induced AKI, we developed three rat models: HS, RM, and their combination (RM-HS). RM-HS resulted in the most severe phenotype, including high mortality, profound metabolic dysfunction, and extensive renal injury.

Bulk and spatial transcriptomics revealed RM as the dominant driver of transcriptional changes, with significant involvement of hypoxia, reactive oxygen species (ROS), unfolded protein response (UPR), and apoptosis pathways. Region-specific analyses highlighted the corticomedullary junction (CMJ) as a critical site of injury, where lipid metabolism dysregulation and ferroptosis were prominent. Notably, perilipin 2 (PLIN2) emerged as a key marker of RM and RM-HS, correlating with metabolic dysfunction and injury severity.