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Fibrosis-Related microRNAs in Crohn's Disease with Fibrostenosis and Inflammatory Stenosis
Miha Jerala1, Tinkara Remic1, Nina Hauptman1
1Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Abstract:
Crohn's disease (CD) is frequently complicated by strictures that can be either inflammatory or fibrostenotic. This distinction is important for deciding the best treatment course, but it can be difficult to determine clinically, sometimes even by advanced imaging techniques. We performed miRNA PCR panel screening on pooled samples of ileum with CD fibrostenosis or inflammatory stenosis. Eight miRNAs with profibrotic (miR-93-5p, miR-376c-3p and miR-424-5p), or fibroprotective (miR-133a-3p, miR-133b, miR-193a-5p, miR-335-5p and miR-378a-3p) functions described in the literature were selected for validation on 20 samples each of CD with fibrostenosis or inflammatory stenosis, with a separate sampling of the submucosa and subserosa. The results showed significant differences between the groups in subserosal samples, with upregulation of profibrotic miRNAs and downregulation of fibroprotective miRNAs in fibrostenosis compared to inflammatory stenosis. Only miR-424-5p showed a significant difference in the submucosa. There were significant differences in miRNA expression between subserosa and submucosa. Our results provide further evidence that the major differences between fibrostenosis and inflammatory stenosis are located in the subserosa, which is inaccessible to endoscopic sampling, highlighting the need for cross-sectional imaging or serological markers. We identify several miRNAs previously not connected to fibrosis in CD, which could potentially serve as biomarkers of fibrostenosis.
Insights
Distinguishing Crohn's disease (CD) strictures is key for treatment. Fibrostenotic CD shows distinct miRNA changes in the subserosa, suggesting potential new biomarkers for fibrosis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Medical Diagnostics
Background:
- Crohn's disease (CD) often leads to strictures, which can be inflammatory or fibrostenotic.
- Differentiating these stricture types is crucial for effective treatment but clinically challenging, even with advanced imaging.
- MicroRNAs (miRNAs) are implicated in fibrotic processes, but their specific roles in CD strictures are not fully elucidated.
Purpose of the Study:
- To investigate miRNA expression differences between inflammatory and fibrostenotic strictures in Crohn's disease.
- To identify potential miRNA biomarkers for distinguishing fibrostenotic strictures.
- To explore the differential expression of miRNAs in the submucosa and subserosa layers of the ileum in CD.
Main Methods:
- miRNA PCR panel screening was performed on pooled ileal samples from CD patients with fibrostenotic or inflammatory stenosis.
- Eight selected miRNAs with known or suspected profibrotic or fibroprotective functions were validated.
- Samples were analyzed separately for submucosa and subserosa layers from 20 cases of each stricture type.
Main Results:
- Significant differences in miRNA expression between fibrostenotic and inflammatory CD strictures were observed in the subserosa.
- Profibrotic miRNAs were upregulated, and fibroprotective miRNAs were downregulated in fibrostenotic strictures within the subserosa.
- Only miR-424-5p showed significant differential expression in the submucosa, while subserosa and submucosa layers exhibited distinct miRNA expression profiles.
Conclusions:
- The subserosa layer displays the most significant miRNA expression differences between fibrostenotic and inflammatory CD strictures.
- These findings suggest that miRNAs, particularly those altered in the subserosa, could serve as novel biomarkers for CD fibrostenosis.
- The inaccessibility of the subserosa for endoscopic sampling underscores the need for alternative diagnostic approaches like cross-sectional imaging or serological markers.
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