Unraveling the Temporal Dynamics of Radiation-Induced Lung Injury

Radiation pneumonitis remains a dose-limiting complication in thoracic radiotherapy, critically impacting treatment efficacy and long-term patient survival. Despite its clinical significance, the dynamic molecular reprogramming underlying radiation-induced lung injury (RILI) progression remains poorly characterized. Utilizing a murine model validated by histopathological analysis, we implemented RNA-seq to systematically map the temporal evolution of RILI at critical phases: acute inflammation, transitional, and fibrotic. Through combining analysis, we identified Ces2e as a pivotal node exhibiting sustained upregulation at both transcriptional and translational levels during early pathogenesis. Functional enrichment revealed time-dependent activation of xenobiotic metabolism and ECM-receptor interaction pathways, with Ces2e overexpression correlating with macrophage polarization and lipid peroxidation accumulation. This temporal multi-omics atlas not only deciphers stage-specific molecular signatures of RILI but also nominates Ces2e as a potential theranostic target for early intervention. Overall design: RNA-seq profiles of lungs from C57BL/6J mice at 4, 8, and 16 weeks after thoracic radiation.