PXD047338 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Pathology-driven epithelial sulfide loss reprograms the redox proteome and triggers Barrett’s esophagus |
| Description | Background & Aims
Barrett’s esophagus (BE), a metaplastic transformation driven by gastroesophageal reflux disease (GERD), induces oxidative stress but the underlying redox mechanisms remain poorly understood. Protein persulfidation (PSSH), a redox-sensitive, reversible, and antioxidative post-translational modification regulated by hydrogen sulfide (H₂S) metabolism, has not been explored in this context. Here, we identify epithelial PSSH as a key regulator of this premalignant process.
Methods
We applied proteomics and chemoproteomics in patients to map and validate PSSH and total proteome profiles across healthy (squamous), GERD-exposed, and metaplastic epithelium. Using in vitro and in vivo models of chronic GERD and BE, we modulated H₂S levels genetically and pharmacologically. Mechanistic and functional effects were assessed using tissue biopsies or recombinant human proteins.
Results
GERD-induced oxidative loss of H₂S and its enhanced catabolism initiated early PSSH proteome remodeling in squamous epithelium, which expanded in BE and affected >1,300 proteins in clinical samples, indicating potential biomarkers. This also included altered persulfidation of enzymes regulating the accumulation of prostaglandin E₂ (PGE₂), a well-established driver of BE development and progression. H₂S depletion accelerated metaplastic transformation, whereas H₂S donors reversed these effects in experimental models. PSSH of 15-hydroxyprostaglandin dehydrogenase (PGDH) reversibly suppressed its activity, protecting the enzyme and, unlike irreversible oxidation, allowing recovery of PGE₂ degradation.
Conclusions
These findings redefine the origin of PGE₂ accumulation in metaplasia and establish sulfide loss and persulfidomic remodeling as central, druggable drivers of epithelial reprogramming and redox imbalance in BE pathogenesis. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-06-04 |
| AnnouncementXML | Submission_2026-06-04_07:35:39.432.xml |
| DigitalObjectIdentifier | https://doi.org/10.6019/PXD047338 |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Thibaut Vignane |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | acetylated residue; monohydroxylated residue |
| Instrument | timsTOF Pro 2 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2023-11-28 08:08:55 | ID requested | |
| 1 | 2026-06-02 19:07:22 | announced | |
| 2 | 2026-06-03 05:20:26 | announced | 2026-06-03: Updated project metadata. |
| ⏵ 3 | 2026-06-04 07:35:40 | announced | 2026-06-04: Updated project metadata. |
Publication List
| Korbut E, Wierdak M, Vignane T, Bakalarz D, Magierowska K, Suski M, Janmaat VT, Hankus J, Glowacka U, Farbaniec M, W, ó, jcik-Grzybek D, Whiteman M, Kukla M, Smits R, Souza RF, Filipovic MR, Magierowski M, Pathology-driven epithelial sulfide loss reprograms the redox proteome and triggers Barrett's esophagus. Gastroenterology, ():(2026) [pubmed] |
| 10.1053/j.gastro.2026.05.016; |
| 10.6019/PXD047338; |
Keyword List
| submitter keyword: persulfidation |
| hydrogen sulfide |
| Barrett’s esophagus |
| gastroesophageal reflux disease (GERD) |
| prostaglandin E2/interleukin 1/mTOR cross-talk |
Contact List
| Milos Filipovic |
|---|
| contact affiliation | SULFAGING group; Leibniz Institute for Analytical Sciences - ISAS - eV. Dortmund, GERMANY |
| contact email | milos.filipovic@isas.de |
| lab head | |
| Thibaut Vignane |
|---|
| contact affiliation | Leibniz-Institut für Analytische Wissenschaften - ISAS,e.V, Dortmund, Germany |
| contact email | thibaut.vignane@outlook.com |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047338
- Label: PRIDE project
- Name: Pathology-driven epithelial sulfide loss reprograms the redox proteome and triggers Barrett’s esophagus
