期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 308, 期 2, 页码 G112-G120出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00132.2013
关键词
fibrosis; liver; vitamin D; collagen; thioacetamide
资金
- Chief Scientist of the Ministry of Health, Israel [3000-4894]
1,25(OH)(2)D-3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)(2)D-3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)(2)D-3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)(2)D-3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)(2)D-3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, alpha-smooth muscle actin (alpha SMA),tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)(2)D-3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)(2)D-3 group compared with the TAA group. 1,25(OH)(2)D-3 significantly inhibited expression of PDGF and TGF-beta by similar to 50% and suppressed the expression of collagen I alpha 1, TIMP1, and alpha-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)(2)D-3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)(2)D-3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)(2)D-3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.
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