In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 3 ( 2022-3-11), p. e0265189-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0265189
DOI:
10.1371/journal.pone.0265189.g001
DOI:
10.1371/journal.pone.0265189.g002
DOI:
10.1371/journal.pone.0265189.g003
DOI:
10.1371/journal.pone.0265189.g004
DOI:
10.1371/journal.pone.0265189.g005
DOI:
10.1371/journal.pone.0265189.g006
DOI:
10.1371/journal.pone.0265189.t001
DOI:
10.1371/journal.pone.0265189.t002
DOI:
10.1371/journal.pone.0265189.t003
DOI:
10.1371/journal.pone.0265189.t004
DOI:
10.1371/journal.pone.0265189.s001
DOI:
10.1371/journal.pone.0265189.s002
DOI:
10.1371/journal.pone.0265189.s003
DOI:
10.1371/journal.pone.0265189.s004
DOI:
10.1371/journal.pone.0265189.s005
DOI:
10.1371/journal.pone.0265189.s006
DOI:
10.1371/journal.pone.0265189.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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