A distinct epigenetic profile distinguishes stenotic from non-inflamed fibroblasts in the ileal mucosa of Crohn’s disease patients

• DOI: 10.1371/journal.pone.0209656
• Publication Date: 2018-12-27T18:33:58Z
• Authors: Andrew Y. F. Li Yim; Jessica R. de Bruyn; Nicolette W. Duijvis; Catriona Sharp; Enrico Ferrero; Wouter J. de Jonge; Manon E. Wildenberg; Marcel M. A. M. M...; Christianne J. Bu...; Geert R. D’Haens; Peter Henneman; Anje A. te Velde
• Keywords: Intestinal mucosa

Background The chronic remitting and relapsing intestinal inflammation characteristic of Crohn's disease frequently leads to fibrosis subsequent stenosis the inflamed region. Approximately a third all patients require resection at some stage in their course. As pathogenesis associated is largely unknown, strong necessity exists better understand pathophysiology thereof. Methods In this study, we investigated changes DNA methylome transcriptome ileum-derived fibroblasts occurrence fibrosis. Eighteen samples were included methylation array twenty-one used for RNA sequencing. Results Most differentially methylated regions expressed genes observed when comparing stenotic with non-inflamed samples. By contrast, few differences non-Crohn's disease, or tissue. Integrative gene expression analyses revealed dysregulation PRKACA E2F1 network, which involved cell cycle progression, angiogenesis, epithelial mesenchymal transition, bile metabolism. Conclusion Our research provides evidence that are systematically dysregulated stenosis-associated fibroblasts.