exacerbates colitis via STAT3 activation induced by Acetyl-CoA accumulation.

Abstract

() has emerged as a potential contributor to ulcerative colitis (UC) pathogenesis, although the specific mechanisms remain incompletely understood. This study demonstrates thatpromotes colitis by disrupting intestinal barrier integrity, inducing apoptosis in epithelial cells, and modulating inflammatory pathways. Furthermore, we demonstrate thatpromotes STAT3 acetylation at K685, followed by phosphorylation at Y705, thereby enhancing its transcriptional activity and exacerbating colitis severity. Additionally,-mediated upregulation of acetyl-CoA levels is responsible for STAT3 acetylation, linking metabolic processes to UC pathophysiology. Pharmacological inhibition of acetyl-CoA production effectively mitigates-induced colitis in experimental models, suggesting potential therapeutic strategies targeting these pathways. These findings unveil a novel regulatory pathway in-associated UC progression and offer new insights for future UC prevention and treatment.