Epigenetic and metabolic reprogramming of fibroblasts in Crohn's disease strictures reveals histone deacetylases as therapeutic targets.

Amy LewisDavid T HumphreysBelen Pan-CastilloGiulio BertiCarla FeliceHannah GordonRadha GadhokAnke NijhuisShameer Mehta SLiliane EleidSidra IqbalAlessandro ArmuzziAnnamaria MinicozziEleni GiannoulatouJoanne ChinAleongRoger FeakinsVirag Sagi-KissDora BarisicMargarita-Ioanna KoufakiJacob G BundyJames O LindsayAndrew Silver

Published in: Journal of Crohn's & colitis (2023)

Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFβ-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis.

Keyphrases

dna methylation
gene expression
genome wide
histone deacetylase
extracellular matrix
single cell
stem cells
liver fibrosis
bone marrow
signaling pathway
tissue engineering
nk cells