Profound gene expression changes in the epithelial monolayer of active ulcerative colitis and Crohn's disease.

Autor: Sæterstad S; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Østvik AE; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.; Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway., Røyset ES; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.; Department of Pathology, St. Olav's University Hospital, Trondheim, Norway., Bakke I; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.; Clinic of Medicine, St Olav's University Hospital, Trondheim, Norway., Sandvik AK; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.; Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway.; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway., Granlund AVB; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.; Clinic of Medicine, St Olav's University Hospital, Trondheim, Norway.; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2022 Mar 11; Vol. 17 (3), pp. e0265189. Date of Electronic Publication: 2022 Mar 11 (Print Publication: 2022).
DOI: 10.1371/journal.pone.0265189
Abstrakt: In recent years it has become apparent that the epithelium is highly involved in inflammatory bowel disease (IBD) pathophysiology. The majority of gene expression studies of IBD are generated from heterogeneous biopsies, providing no distinction between immune cells, the epithelium and other mucosal cells. By using laser capture microdissection (LCM) coupled with RNA sequencing, we aimed to characterize the expressional changes of the isolated colonic epithelial monolayer from ulcerative colitis (UC) and Crohn's disease (CD) patients compared to healthy controls (HC). The analysis identified 3706 genes as differentially expressed between active IBD epithelium and HC. Weighted gene co-expression network analysis was used to stratify genes into modules, which were subsequently characterized using enrichment analysis. Our data show a distinct upregulation of the antigen presentation machinery during inflammation, including major histocompatibility complex class II molecules (e.g. HLA-DPA1, HLA-DPB1, HLA-DRA) and key transcription factors/activators (STAT1, IRF1, CIITA). We also see an epithelial downregulation of retinoic acid-responsive nuclear receptors (RARA, RARB, RXRA), but upregulation of retinoid-metabolizing enzymes (RDH11, ALDH1A2, ALDH1A3), which together suggest a perturbation of epithelial vitamin A signaling during active IBD. Lastly, we identified a cluster of stress-related genes, including activator protein 1 components JUNB and ATF3, as significantly upregulated in active UC but not in CD, revealing an interesting aspect of IBD heterogeneity. The results represent a unique resource for enhanced understanding of epithelial involvement in IBD inflammation and is a valuable tool for further studies on these processes.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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