PXD047338-1

PXD047338 is an original dataset announced via ProteomeXchange.

Title	Persulfidation - a missing key in the fundamental and clinical interpretation of Barrett’s esophagus
Description	Barrett’s esophagus (BE) is a precancerous consequence of gastroesophageal reflux disease (GERD) where metaplastic epithelium replaces squamous mucosa. Mechanisms driving this transformation still remain unclear. Posttranslational proteins persulfidation emerged significant in aging and cardiovascular system, but their role in gastrointestinal (GI) disorders remains unknown. Persulfidation relies on the endogenous hydrogen sulfide (H2S) signaling. We hypothesized that pathway-specific persulfidation impairments underlie BE pathogenesis. We aimed to assess if H2S-bioavailability restoration/depletion impacts persulfidation-sensitive targets and BE development. Methods We analyzed total and persulfidated proteome in 3-sets of clinical biopsies representing BE and squamous epithelium +/- GERD. We implemented an animal model of GERD and BE, generating esophago-gastroduodenal anastomosis (EGDA), followed by 10-weeks-long treatments with H2S donors/inhibitors. We assessed gastric secretion in rats. We employed in vitro human-derived healthy (EPC2), GERD-exposed (NES-G2T) and Barrett’s (BAR-T) cells +/- CRISPR-Cas9-induced H2S-producing enzymes knockouts. Results GERD-induced clinical persulfidation changes in squamous epithelium expanded in BE. Persulfidations of interleukin (IL)-1, prostaglandin (PG)E2 and mTOR signaling, but not exclusively, were impaired. GERD decreased H2S bioavailability in rats esophagus and human squamous, but not metaplastic cells. H2S, reconstituted by i.g. treatment with NaHS or GYY4137, inhibited gastric secretion, metaplasia development, nucleic acids oxidation, IL-1/PGE2/mTOR activation, restoring mucosal microcirculation. H2S-enzymes inactivation accelerated morphological and molecular turnover. Total proteome clustering indicated, among others, NAD(P)H quinone dehydrogenase 1 as an early BE biomarker. GERD-altered persulfidation in squamous epithelium initiate Barrett’s metaplasia, as the mechanistic outcome of reduced H2S bioavailability. Stable H2S biosynthesis and enriched persulfidation switch reflect the adaptative GERD-resistance of the metaplastic epithelium. H2S counteracts BE development by mechanistically interfering with metaplasia-activating IL-1β/PGE2/mTOR pathways.
HostingRepository	PRIDE
AnnounceDate	2026-06-03
AnnouncementXML	Submission_2026-06-02_19:07:21.540.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

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.

10.6019/PXD047338;

submitter keyword: persulfidation

hydrogen sulfide

Barrett’s esophagus

gastroesophageal reflux disease (GERD)

prostaglandin E2/interleukin 1/mTOR cross-talk

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

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PRIDE project URI

• PRIDE
  1. PXD047338
     1. Label: PRIDE project
     2. Name: Persulfidation - a missing key in the fundamental and clinical interpretation of Barrett’s esophagus