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 &mgr;g/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 I. After 4 days of culture, HSCs had DNA synthesis and a high concentration (2000 &mgr;g/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 &mgr;g/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.
Aoyagi
Mariko
M
Department of Gastroenterology and Hepatology, School of Medicine, Yamaguchi University, Minami Kogushi 1-1-1, Ube, 755-8505, Yamaguchi, Japan
Sakaida
Isao
I
Suzuki
Chieko
C
Segawa
Makoto
M
Fukumoto
Yohei
Y
Okita
Kiwamu
K