Pathology-Driven Epithelial Sulfide Loss Reprograms the Redox Proteome and Triggers Barrett's Esophagus.

GERD-associated epithelial loss of hydrogen sulfide triggers early persulfidation (PSSH) proteome remodeling in squamous epithelium, expanding to affect >1300 proteins in Barrett’s esophagus samples.

• Why it matters: Oxidative stress is linked to Barrett’s esophagus, but the redox mechanisms and druggable regulators driving epithelial reprogramming and PGE 2 accumulation are unclear.
• What they did: The study used proteomics and chemoproteomics in 2 patient cohorts across healthy, GERD-exposed, and metaplastic epithelium, then modulated H 2 S genetically and pharmacologically in chronic GERD and BE models.
• The result: H 2 S depletion accelerated metaplastic transformation, while H 2 S donors reversed effects; PSSH of 15-hydroxyprostaglandin dehydrogenase reversibly suppressed activity, enabling recovery of PGE 2 degradation.

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