ArticleInflammatory bowel diseases2020
Murine Precision-cut Intestinal Slices as a Potential Screening Tool for Antifibrotic Drugs.
Article in Inflammatory bowel diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Alternatives to animal models in gastroenterology and hepatology research.Frontiers in pharmacology · 2026Review
- Novel anti-pyroptosis drug loaded on metal-organic framework for intervertebral disc degeneration therapy.Materials today. Bio · 2025Article
- How to Evaluate Fibrosis in IBD?Diagnostics (Basel, Switzerland) · 2023Review
- Prevention and Treatment of Stricturing Crohn's Disease - Perspectives and Challenges.Expert review of gastroenterology & hepatology · 2021Review
- Mycobacterial Hsp65 antigen delivered by invasive Lactococcus lactis reduces intestinal inflammation and fibrosis in TNBS-induced chronic colitis model.Scientific reports · 2020Article
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Authors and funding
9 authors at 1 institution in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntestinal fibrosis is a hallmark of Crohn's disease. Here, we investigated the impact of several putative antifibrotic compounds on the expression of fibrosis markers using murine precision-cut intestinal slices.
methodsMurine precision-cut intestinal slices were cultured for 48 hours in the presence of profibrotic and/or antifibrotic compounds. The fibrotic process was studied on gene and protein level using procollagen 1a1 (Col1α1), heat shock protein 47 (Hsp47), fibronectin (Fn2), and plasminogen activator inhibitor-1 (Pai-1). The effects of potential antifibrotic drugs mainly inhibiting the transforming growth factor β (TGF-β) pathway (eg, valproic acid, tetrandrine, pirfenidone, SB203580, and LY2109761) and compounds mainly acting on the platelet-derived growth factor (PDGF) pathway (eg, imatinib, sorafenib, and sunitinib) were assessed in the model at nontoxic concentrations.
resultsMurine precision-cut intestinal slices remained viable for 48 hours, and an increased expression of fibrosis markers was observed during culture, including Hsp47, Fn2, and Pai-1. Furthermore, TGF-β1 stimulated fibrogenesis, whereas PDGF did not have an effect. Regarding the tested antifibrotics, pirfenidone, LY2109761, and sunitinib had the most pronounced impact on the expression of fibrosis markers, both in the absence and presence of profibrotic factors, as illustrated by reduced levels of Col1α1, Hsp47, Fn2, and Pai-1 after treatment. Moreover, sunitinib significantly reduced Hsp47 and Fn2 protein expression and the excretion of procollagen 1.
conclusionsPrecision-cut intestinal slices can successfully be used as a potential preclinical screening tool for antifibrotic drugs. We demonstrated that sunitinib reduced the expression of several fibrosis markers, warranting further evaluation of this compound for the treatment of intestinal fibrosis.
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