Publication Name	World Journal of Gastroenterology
Manuscript ID	120856
DOI	10.3748/wjg.120856
Country	Belgium

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Epithelial endoplasmic reticulum stress drives intestinal fibrogenesis in ulcerative colitis: Retrospective analysis and profibrogenic organoid model development
Manuscript Source	Unsolicited Manuscript
All Author List	Marty J Stepniak, Pierre Adam, Charlotte Massot, Catherine Salée, Sophie Vieujean, Catherine Reenaers, Jean-Philippe Loly, Carla Coimbra Marques, Emmanuel Decker, Philippe Delvenne, Silvia Speca, Stephanie Beq, Noëlla Blétard, Edouard Louis and Marie-Alice Meuwis
Funding Agency and Grant Number	Funding Agency Grant Number FNRS/FRIA No. 40014792 FNRS/FRIA No. 40029541
Corresponding Author	Marty J Stepniak, Department of Translational Gastroenterology, University of Liège, Avenue de l'hôpital 11, GIGA B34 /+2, Liège 4000, Province de Liège, Belgium. mstepniak@uliege.be
Key Words	Ulcerative colitis; Intestinal fibrosis; Intestinal apical-out organoids; Primary fibroblasts; Tunicamycin; Endoplasmic reticulum stress; Epithelial response
Core Tip	Evidences on the epithelium contribution to ulcerative colitis (UC) intestinal fibrosis progression are scarce. We show that epithelial endoplasmic reticulum stress (ERS) and anterior gradient protein 2 homolog (AGR2) associate with fibro-inflammatory remodeling in UC surgical tissues. In patient-derived apical-out organoids, transient tunicamycin-induced ERS triggers sustained AGR2 upregulation and secretion, generating a paracrine profibrogenic signal inducing fibroblast-to-myofibroblast transition, without proinflammatory nor profibrotic cytokine. This translational model links epithelial ERS response to fibroblast-to-myofibroblast transition and secreted AGR2, in the absence of inflammatory triggers. This model provides a platform to discover potential epithelial biomarkers, therapeutic targets and test antifibrotic strategies in this specific context mimicking possible fibrosis progression independently of inflammation.
Citation	Stepniak MJ, Adam P, Massot C, Salée C, Vieujean S, Reenaers C, Loly JP, Coimbra Marques C, Decker E, Delvenne P, Speca S, Beq S, Blétard N, Louis E, Meuwis MA. Epithelial endoplasmic reticulum stress drives intestinal fibrogenesis in ulcerative colitis: Retrospective analysis and profibrogenic organoid model development. World J Gastroenterol 2026; In press DOI: https://doi.org/10.3748/wjg.120856
PDF	120856-in-press.pdf

Received	2026-03-11 01:10
Peer-Review Started	2026-03-11 01:11
First Decision by Editorial Office Director	2026-03-28 03:16
Return for Revision	2026-03-28 03:16
Revised	2026-04-25 19:05
Publication Fee Transferred	2026-05-12 08:19
Second Decision by Editor	2026-11-02 02:19
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-11-04 09:59
Articles in Press	2026-11-04 09:59
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1007-9327 (print) and 2219-2840 (online)
Open Access	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
Copyright	©Author(s) (or their employer(s)) 2026. No commercial re-use. See Permissions. Published by Baishideng Publishing Group Inc.
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