Multi-parameter magnetic resonance imaging of zebularine in liver fibrosis treatment and calcineurin/ mechanism.

BACKGROUND

Hepatic stellate cell (HSC) activation is key to liver fibrosis. Targeting DNA methylation shows promise. Zebularine, a methylation inhibitor, may suppress HSC activation the calcineurin (CaN)/ pathway. Magnetic resonance imaging (MRI) is a noninvasive tool for evaluating liver fibrosis evaluation tool, but multiparametric MRI for zebularine's effects in liver fibrosis mouse models has not been studied.

AIM

To clarify the anti-fibrosis mechanism and MRI-evaluated efficacy of zebularine.

METHODS

, transforming growth factor (TGF)-β1-stimulated human HSCs (LX-2) were treated with zebularine. α-smooth muscle actin, fibrotic and anti-fibrotic gene levels, and regulator of calcineurin1 (RCAN1) regulation were measured. , carbon tetrachloride (CCl)-induced liver fibrosis in mice was treated with zebularine, and fibrosis was evaluated using various biochemical, histopathological, and MRI methods.

RESULTS

Zebularine upregulated RCAN1.4 protein ( < 0.01) and inhibited the CaN/ pathway ( < 0.05). In HSCs, TGF-β1 reduced anti-fibrotic gene massage RNA (mRNA) and increased fibrotic mRNA ( < 0.05), whereas zebularine had the opposite effects ( < 0.01, < 0.05). CCl-treated mice exhibited increases in various fibrosis-related indices, all of which were reversed by zebularine treatment ( < 0.05).

CONCLUSION

Zebularine may reduce LX-2 activation and extracellular matrix deposition RCAN1.4 and CaN/ pathways. Multiparametric MRI can assess its efficacy, suggesting zebularine's potential as a liver fibrosis treatment.