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Volume 14
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Review

Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets

by
Fotios S. Fousekis
1,*,
Konstantinos Mpakogiannis
1,
Ioanna Nefeli Mastorogianni
1,
Georgios D. Lianos
2,
Dimitrios K. Christodoulou
1 and
Konstantinos H. Katsanos
1
1
Department of Gastroenterology and Hepatology, University Hospital of Ioannina, University of Ioannina, 45110 Ioannina, Greece
2
Department of Surgery, University Hospital of Ioannina, 45110 Ioannina, Greece
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(12), 4060; https://doi.org/10.3390/jcm14124060 (registering DOI)
Submission received: 6 May 2025 / Revised: 1 June 2025 / Accepted: 6 June 2025 / Published: 8 June 2025
(This article belongs to the Special Issue Novel Therapeutic Targets with Inflammatory Bowel Diseases)
Versions Notes

Abstract

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions between immune cells, mesenchymal cells, cytokines, and the gut microbiota. Key fibrogenic mechanisms include the activation of fibroblasts and myofibroblasts, cytokine signaling, and disrupted turnover of the extracellular matrix. Advancements in imaging techniques, such as MRI and CT enterography, have improved the detection and monitoring of fibrosis. Additionally, molecular techniques targeting fibroblast activation proteins show promise as a new imaging method. However, there are currently no approved anti-fibrotic therapies for CD. Emerging strategies focus on key pathways and novel therapeutic targets, including growth factor modulators, intracellular enzyme and kinases modulators, and interventions targeting the modulation of inflammation and extracellular matrix, which are being evaluated in preclinical and clinical settings. This review discusses the pathophysiology, diagnostic advancements, and therapeutic perspectives related to intestinal fibrosis in CD, emphasizing the urgent need for targeted anti-fibrotic therapies to prevent long-term complications and improve the life quality of patients.
Keywords: Crohn’s disease; intestinal fibrosis; extracellular matrix; anti-fibrotic therapy Crohn’s disease; intestinal fibrosis; extracellular matrix; anti-fibrotic therapy

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MDPI and ACS Style

Fousekis, F.S.; Mpakogiannis, K.; Mastorogianni, I.N.; Lianos, G.D.; Christodoulou, D.K.; Katsanos, K.H. Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets. J. Clin. Med. 2025, 14, 4060. https://doi.org/10.3390/jcm14124060

AMA Style

Fousekis FS, Mpakogiannis K, Mastorogianni IN, Lianos GD, Christodoulou DK, Katsanos KH. Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets. Journal of Clinical Medicine. 2025; 14(12):4060. https://doi.org/10.3390/jcm14124060

Chicago/Turabian Style

Fousekis, Fotios S., Konstantinos Mpakogiannis, Ioanna Nefeli Mastorogianni, Georgios D. Lianos, Dimitrios K. Christodoulou, and Konstantinos H. Katsanos. 2025. "Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets" Journal of Clinical Medicine 14, no. 12: 4060. https://doi.org/10.3390/jcm14124060

APA Style

Fousekis, F. S., Mpakogiannis, K., Mastorogianni, I. N., Lianos, G. D., Christodoulou, D. K., & Katsanos, K. H. (2025). Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets. Journal of Clinical Medicine, 14(12), 4060. https://doi.org/10.3390/jcm14124060

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