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• W3082675235 endingPage "175628482095257" @default.
• W3082675235 startingPage "175628482095257" @default.
• W3082675235 abstract "Background and Aims: Crohn’s disease (CD) can be complicated by intestinal fibrosis. Pharmacological therapies against intestinal fibrosis are not available. The aim of this study was to determine whether pathways involved in collagen metabolism are upregulated in intestinal fibrosis, and to discuss which drugs might be suitable to inhibit excessive extracellular matrix formation targeting these pathways. Methods: Human fibrotic and non-fibrotic terminal ileum was obtained from patients with CD undergoing ileocecal resection due to stenosis. Genes involved in collagen metabolism were analyzed using a microfluidic low-density TaqMan array. A literature search was performed to find potential anti-fibrotic drugs that target proteins/enzymes involved in collagen synthesis, its degradation and its recognition. Results: mRNA expression of collagen type I ( COL1A1, 0.76 ± 0.28 versus 37.82 ± 49.85, p = 0.02) and III ( COL3A1, 2.01 ± 2.61 versus 68.65 ± 84.07, p = 0.02) was increased in fibrotic CD compared with non-fibrotic CD. mRNA expression of proteins involved in both intra- and extracellular post-translational modification of collagens (prolyl- and lysyl hydroxylases, lysyl oxidases, chaperones), collagen-degrading enzymes (MMPs and cathepsin-K), and collagen receptors were upregulated in the fibrosis-affected part. A literature search on the upregulated genes revealed several potential anti-fibrotic drugs. Conclusion: Expression of genes involved in collagen metabolism in intestinal fibrosis affected terminal ileum of patients with CD reveals a plethora of drug targets. Inhibition of post-translational modification and altering collagen metabolism might attenuate fibrosis formation in the intestine in CD. Which compound has the highest potential depends on a combination anti-fibrotic efficacy and safety, especially since some of the enzymes play key roles in the physiology of collagen." @default.
• W3082675235 created "2020-09-08" @default.
• W3082675235 creator A5023039423 @default.
• W3082675235 creator A5023853436 @default.
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• W3082675235 creator A5064007764 @default.
• W3082675235 creator A5068944242 @default.
• W3082675235 creator A5071144290 @default.
• W3082675235 date "2020-01-01" @default.
• W3082675235 modified "2023-10-14" @default.
• W3082675235 title "Intestinal stenosis in Crohn’s disease shows a generalized upregulation of genes involved in collagen metabolism and recognition that could serve as novel anti-fibrotic drug targets" @default.
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