Role of cyclooxygenase 2 and its inhibitor valdecoxib in liver fibrosis

Abstract

To explore the effects of cyclooxygenase-2 (COX-2) and its inhibitor valdecoxib in liver fibrosis. Hepatic fibrosis was induced by carbon tetrachloride for 8 weeks in wild-type and COX-2 knockout mice. And the levels of hyaluronic acid (HA), collagen IV(IV-C), procollagen III(PCIII) and α-smooth muscle actin (α-SMA ) were determined. Cyclin D and cyclin E were measured in hepatic satellite cell (HSC) after a treatment of valdecoxib for 24 h or not. HA, IV-C, PCIII and α-SMA all had significant difference in 3 groups (control group:(180 ± 13) µg/L, (56 ± 9) µg/L, (39 ± 13) µg/L, 2.49% ± 0.24% in control, F = 78.52, 61.30, 41.96, 28.15, all P < 0.05) . HA, IV-C and α-SMA in wild-type liver fibrosis mice were higher than those in knockout counterparts ((413 ± 60) vs (308 ± 42) µg/L, (96 ± 13) vs (74 ± 10 ) µg/L, 8.99% ± 0.81% vs 4.72% ± 0.50%, all P < 0.01). But PCIII were similar between two groups ((82 ± 12) vs (72 ± 15) µg/L, P = 0.06). Wild-type mice expressed higher levels of cyclin D and cyclin E than those of knockout mice (0.96 ± 0.15 vs 0.76 ± 0.10, 0.94 ± 0.13 vs 0.82 ± 0.09, P = 0.02, 0.04). The rates of cyclin D and cyclin E were 0.40 ± 0.06 and 0.38 ± 0.05, 0.35 ± 0.04 and 0.37 ± 0.06 respectively after a treatment of valdecoxib. And both deceased in hepatic satellite cell of wild-type and knockout mice (both P < 0.01) versus those without valdecoxib. COX-2 increases the activation and proliferation of HSC leading to liver fibrosis. And its inhibitor may depress liver fibrosis by decreasing the expressions of cyclin D and cyclin E in COX-2 dependent and(or) independent way.