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ResearchIn-Press PreviewGastroenterologyInflammation Open Access | 10.1172/JCI192804

Meflin confers antifibrotic properties to intestinal fibroblasts in inflammatory bowel disease

Jingxi Mu,1 Keiko Maeda,1 Tadashi Iida,1 Shinji Mii,2 Nobutoshi Esaki,2 Yukihiro Shiraki,2 Yasuyuki Mizutani,1 Masanao Nakamura,3 Takeshi Yamamura,1 Tsunaki Sawada,3 Eri Ishikawa,1 Kentaro Murate,1 Takashi Hirose,1 Kazuhiro Furukawa,1 Akina Oishi,1 Haruhiko Suzuki,4 Takayoshi Kishida,5 Goro Nakayama,5 Mitsuhiro Fujishiro,6 Hiroki Kawashima,1 and Atsushi Enomoto2

1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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1Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan

2Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

3Department of Endoscopy, Nagoya University Graduate School of Medicine, Nagoya, Japan

4Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan

5Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

6Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

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Published May 19, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI192804.
Copyright © 2026, Mu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 19, 2026 - Version history
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Abstract

Dysfunctional intestinal fibrosis is an irreversible complication of Crohn’s disease (CD), The complex heterogeneity of intestinal mesenchymal cells makes it difficult to understand the pathogenesis of intestinal fibrosis. Previously, we identified Meflin as a marker of fibroblast subsets. This study aimed to explore the role of Meflin-positive fibroblasts in intestinal fibrogenesis and investigate the potential of pharmacological control of Meflin expression as a treatment for patients with CD. Our results indicated that Meflin expression was upregulated in fibroblasts at the early stage of fibrosis but was downregulated in established fibrosis in both patients with CD and two different mouse models, which are the chronic dextran sodium sulfate (DSS) model and an interleukin-10-deficient model that spontaneously develops intestinal inflammation. Meflin-deficient mice exacerbated intestinal fibrosis with dysregulated expression of non-canonical Wnt ligand WNT5A and its receptor ROR2. Pharmacologically induced Meflin expression through the administration of a synthetic retinoid reversed intestinal fibrosis in the DSS model and suppressed pro-fibrotic protein secretion in fibroblasts isolated from patients with CD. Our findings indicate that Meflin-positive fibroblasts represent a functional subpopulation that suppresses intestinal fibrosis. Augmentation of Meflin expression shows antifibrotic effects and holds promise as a therapeutic approach for intestinal fibrosis in patients with CD.

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  • Version 1 (May 19, 2026): In-Press Preview
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