DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis
Permanent lenke
https://hdl.handle.net/10037/21777Dato
2021-04-01Type
Journal articleTidsskriftartikkel
Peer reviewed
Forfatter
Taman, Hagar; Fenton, Christopher Graham; Anderssen, Endre; Florholmen, Jon; Paulssen, Ruth HSammendrag
Severe ulcerative colitis (UC) is a potentially life-threatening disease with a potential colorectal cancer (CRC) risk. The aim of this study was to explore the relationship between transcriptomic and genome-wide DNA methylation profiles in a well-stratified, treatment-naïve severe UC patient population in order to define specific epigenetic changes that could be responsible for the grade of disease severity. Mucosal biopsies from treatment-naïve severe UC patients (n = 8), treatment-naïve mild UC (n = 8), and healthy controls (n = 8) underwent both whole transcriptome RNA-Seq and genome-wide DNA bisulfite- sequencing, and principal component analysis (PCA), cell deconvolutions and diverse statistical methods were applied to obtain a dataset of significantly differentially expressed genes (DEGs) with correlation to DNA methylation for severe UC. DNA hypo-methylation correlated with approximately 80% of all DEGs in severe UC when compared to mild UC. Enriched pathways of annotated hypo-methylated genes revealed neutrophil degranulation, and immuno-regulatory interactions of the lymphoid system. Specifically, hypo-methylated anti-inflammatory genes found for severe UC were IL10, SIGLEC5, CD86, CLMP and members of inflammasomes NLRP3 and NLRC4. Hypo-methylation of anti-inflammatory genes during severe UC implies an interplay between the epithelium and lamina propria in order to mitigate inflammation in the gut. The specifically DNA hypo-methylated genes found for severe UC can potentially be useful biomarkers for determining disease severity and in the development of new targeted treatment strategies for severe UC patients.
Er en del av
Taman, H. (2022). Epigenetics in Inflammatory Bowel Disease. Contribution of DNA methylation to Ulcerative Colitis pathogenesis. (Doctoral thesis). https://hdl.handle.net/10037/24490.Forlag
Public Library of ScienceSitering
Taman HM, Fenton CG, Anderssen E, Florholmen J, Paulssen RH. DNA hypo-methylation facilitates anti-inflammatory responses in severe ulcerative colitis. PLOS ONE. 2021;16(4):1-17Metadata
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