Background and aims: 1,25(OH)2D3, the active form of vitamin D was found by us to have anti-proliferative and anti-fibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo.Methods: The anti-fibrotic effect of 1,25(OH)2D3 was investigated in thioacetamide (TAA) model and in a bile duct ligation model. In the preventive model, rats received simultaneously intra-peritoneum injection of TAA and/or 1,25(OH)2D3, for 10 weeks. In the remedial model, rats were treated with TAA for 10 weeks and then received 1,25(OH)2D3 or saline for eight weeks. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (αSMA), tissue inhibitor of metalloproteinase (TIMP1), platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β) expression were measured by western blot analysis and real-time PCR.
Results: Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of TAA+1,25(OH)2D3 group compared to the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ~50% and suppressed the expression of collagen Iα1, TIMP1 and αSMA by ~3, 2, 3 fold, respectively. In contrast, 1,25(OH)2D3 was inefficient to ameliorate established liver fibrosis. Furthermore, administration of 1,25(OH)2D3 to BDL rats, led to high mortality rate probably caused by hypercalcemia. Conclusion: 1,25(OH)2D3 may be considered as a potential preventive treatment of liver cirrhosis.
