Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn's Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets.

ABSTRACT:

Background and aims

No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterized fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies.

Methods

We undertook immunohistochemistry, metabolic, signalling pathway and epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/NSCD fibroblasts were cultured with TGFβ and valproic acid [VPA].

Results

Stricturing CD was characterized by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1

SUBMITTER: Lewis A 

PROVIDER: S-EPMC11147807 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature