Intestinal Fibrosis in Crohn’s Disease: Pathophysiology, Diagnosis, and New Therapeutic Targets
Abstract
:1. Introduction
2. Literature Research
3. Mechanisms of Fibrosis in Crohn’s Disease
3.1. Cells Involved in Intestinal Fibrosis
3.2. Molecular Mechanisms in Intestinal Fibrosis
3.3. Alterations of Extracellular Matrix
3.4. Creeping Fat
3.5. Gut Microbiota and Intestinal Fibrosis
4. Diagnosis of Intestinal Fibrosis
5. Anti-Fibrotic Treatment and Novel Targets
5.1. Growth Factor Modulators
5.1.1. TGF-β Inhibitors
5.1.2. Connective Tissue Growth Factor Inhibitors
5.1.3. Fibroblast Growth Factor Analogues
5.2. Intracellular Enzymes and Kinases
5.3. Inflammation Modulators
5.4. Extracellular Matrix Modulators
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Component | Biological Mediators and Features | Pathogenic Role | Ref. |
---|---|---|---|
Cellular Components |
| Produce ECM; sustain inflammation and promote fibrosis | [11,12,13,14,15] |
Cytokines, Melanocortin System and Growth Factors |
| Regulate fibroblast activation, collagen synthesis, and ECM turnover | [16,17,18,19,20] |
ECM Remodeling |
| Alters tissue architecture; favors chronic fibrotic progression | [21,22,23] |
Creeping Fat |
| Amplifies inflammation; promotes ECM production and immune cell recruitment | [24,25,26] |
Gut Microbiota |
| Triggers innate immune pathways and myofibroblast activation | [27,28,29,30] |
Diagnostic Method | Advantages | Limitations |
---|---|---|
Endoscopy with biopsy | Gold standard; allows histological analysis, detection of neoplastic lesions, and assessment of CD activity | Expensive; not always widely available; advanced sequences may require expertise |
Magnetic resonance imaging (MRI) | High-resolution imaging; native T1 mapping and magnetization transfer imaging improve fibrosis grading | Expensive; not always widely available; advanced sequences may require expertise |
Ultrasound (contrast-enhanced, elastography) | Non-invasive and accessible; can differentiate inflammatory vs. fibrotic strictures | Operator- and patient-dependent; limited by bowel gas and anatomic constraints |
Computed Tomographic Enterography (CTE) | Enhanced by spectral CT and 3D printing; radiomic and machine learning analysis outperforms radiologist assessment | Radiation exposure; needs standardization for fibrosis-specific interpretation |
Molecular imaging (FAPI-PET/CT) | Targets FAP expression; may distinguish fibrosis from inflammation with high specificity | Still experimental; requires further clinical validation |
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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
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 StyleFousekis, 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 StyleFousekis, 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