COPD Preferentially Disrupts Constitutive Redox Support Relative to Inducible Antioxidant Defense
Redox homeostasis requires both inducible antioxidant defense and constitutive machinery that continuously regenerates cellular reducing capacity. How these systems are altered across lung cell populations in chronic obstructive pulmonary disease (COPD) remains unclear. We integrated donor-level single-nucleus lung transcriptomes with smoke-exposure models, independent cohorts, and large-scale…
Chronic Obstructive Pulmonary Disease (COPD) exhibits a preferential disruption in constitutive redox support compared to inducible antioxidant defense, according to a recent study. This redox homeostasis relies on both inducible antioxidant defense and constitutive machinery that constantly regenerates cellular reducing capacity.
Researchers analyzed single-nucleus lung transcriptomes, independent cohorts, and pharmacologic perturbation data to investigate the impact of COPD on these redox programs. The study found that both redox programs were diminished in established COPD, but constitutive redox support was affected more significantly, particularly in fibroblasts and lymphatic endothelium.
Among 515 regulator programs, PGC-1 target-program output showed the most negative effect in fibroblasts, despite preserved PPARGC1A expression. While smoke exposure activated the inducible antioxidant defense across experimental models, this adaptive program was reduced in established COPD. Pharmacologic perturbations further distinguished the two redox arms, revealing that redox-directed interventions yielded larger transcriptional responses in inducible defense, while constitutive support increased along with PGC-1 target output.
Notably, fibroblasts in COPD displayed a distinct redox phenotype, marked by reduced PGC-1 target-program output.
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