Prolyl 4-hydroxylase inhibitor is more effective for the inhibition of proliferation than for inhibition of collagen synthesis of rat hepatic stellate cells

The aim of this study was to investigate whether a prolyl 4-hydroxylase inhibitor (HOE 077) prevents the proliferation and collagen synthesis of rat hepatic stellate cells (HSCs). Rat HSCs were isolated and cultured with 100, 500, 1000 or 2000 mug/ml of HOE 077 with or without hepatocytes. After 4 day culture, the cell cycle of HSCs was examined by flow cytometry along with messenger RNA expression of procollagen type 1. After 4 days of culture, HSCs had DNA synthesis and a high concentration (2000 mug/ml) of HOE 077 significantly reduced this DNA synthesis. However, HOE 077 incubated with hepatocytes could significantly reduce mitosis at a lower concentration of HOE077 (500 mug/ml) without significant reduction of alpha(2)(I) procollagen mRNA expression. These results indicate that the prolyl 4-hydroxylase inhibitor is more effective for the inhibition of proliferation than for inhibition of collagen synthesis of HSCs. (C) 2002 Elsevier Science B.V. All rights reserved.