Sodium butyrate attenuates liver fibrogenesis via promoting H4K8 crotonylation.

Sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor derived from dietary sources, demonstrates its potential in improving liver fibrosis in mice. This study explored NaB's impact on liver fibrosis through histone crotonylation. In vitro, NaB significantly inhibited the growth of TGF-β-stimulated LX2 hepatic stellate cells and reduced the expression of fibrotic markers ACTA2, the encoding gene of αSMA, and COL1A1 proportionally to the dosage. In vivo, NaB treatment of CCl-induced ICR mice led to notable gains in liver function and a marked suppression in liver fibrosis. NaB inhibited Hdac2 and Hdac3 expression leading to increased H4K8 crotonylation, and modulated key fibrosis-related genes, providing a mechanistic basis for its therapeutic potential. Trichostatin A (TSA) exhibited similar effects to NaB, supporting the importance of HDAC inhibition in modulating these pathways. Overall, NaB's modulation of HDAC activity and histone crotonylation reveals a novel mechanism underlying its impact on liver fibrosis, highlighting its promise as a treatment for liver disease.