Intestinal subepithelial myofibroblasts in inflammatory bowel disease: fibroblast heterogeneity, fibrosis, and therapeutic targeting.

Authors

Fang Li, Chao Xu, Jun Chen, Teng Lei, Xigui Tian, Yuanling Zhang, Guoqing Chen

Published in

Frontiers in medicine. Volume 13. Pages 1808431. Epub Jun 24, 2026.

Abstract

Intestinal fibrosis remains one of the most challenging complications of inflammatory bowel disease (IBD), frequently leading to bowel strictures, impaired intestinal function, and surgical intervention. Among the stromal cell populations involved in intestinal remodeling, intestinal subepithelial myofibroblasts (ISEMFs) have emerged as central regulators of epithelial homeostasis, mucosal repair, immune responses, and extracellular matrix remodeling. However, persistent inflammatory and microbial stimuli can drive pathological ISEMF activation, resulting in excessive matrix deposition and progressive fibrosis. This review aims to provide a comprehensive overview of the physiological and pathological roles of ISEMFs in IBD. We first discuss their functions in maintaining epithelial integrity, supporting the intestinal stem-cell niche, and coordinating tissue repair. We then examine the mechanisms underlying ISEMF activation during chronic inflammation, focusing on immune-stromal crosstalk, profibrotic cytokines, mechanotransduction, metabolic reprogramming, and key signaling pathways including TGF-β/Smad, JAK/STAT, and Wnt/β-catenin. Particular attention is given to recent advances in single-cell and spatial transcriptomics that have revealed marked fibroblast heterogeneity and identified pathogenic fibroblast subsets associated with fibrostenotic disease. Finally, we summarize current and emerging therapeutic strategies targeting stromal pathways, including antifibrotic agents, cytokine-directed therapies, fibroblast subset-specific interventions, and biomarker-guided precision approaches. By integrating advances in stromal biology, fibrosis mechanisms, and translational therapeutics, this review highlights ISEMFs as key drivers of intestinal fibrosis and promising targets for future disease-modifying therapies in IBD.

PMID:
42422813
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.