Hui Alex Yui, Cheng Alfred Sze-Lok, Chan Henry Lik-Yuen, Go Minnie Yin-Yin, Chan Francis Ka-Leung, Sakata Ryuichiro, Ueno Takato, Sata Michio, Sung Joseph Jao-Yiu
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
Prostaglandins Leukot Essent Fatty Acids. 2004 Nov;71(5):329-33. doi: 10.1016/j.plefa.2004.04.007.
Hepatic stellate cells (HSC) are central to liver fibrosis. The eicosanoid pathway and cyclooxygenase-2 (COX-2) may be an important signaling mechanism in HSC. We investigated the role of COX-2, prostaglandin E(2) (PGE(2)) and prostaglandin I(2) (PGI(2)) in proliferation of LI90, an immortalized cell line of HSC. Our results showed that COX-2 was upregulated by platelet-derived growth factor (PDGF), a mitogen in HSC. COX-2 was responsible for the production of PGE(2) and PGI(2) in PDGF-stimulated LI90 cells. Furthermore, we demonstrated that COX-2 and PGE(2) mediated the proliferative response of LI90 to PDGF while synthetic analogue of PGI(2) exhibited anti-proliferative effect. Our findings suggest complex interactions of prostaglandins in liver fibrogenesis. In vivo studies using animal models are needed to elucidate the effect of COX-2 inhibition by non-steroidal anti-inflammatory drugs or COX-2 inhibitor in hepatic fibrosis.
肝星状细胞（HSC）是肝纤维化的核心。类花生酸途径和环氧化酶-2（COX-2）可能是HSC中的一种重要信号机制。我们研究了COX-2、前列腺素E2（PGE2）和前列腺素I2（PGI2）在永生化HSC细胞系LI90增殖中的作用。我们的结果表明，COX-2被血小板衍生生长因子（PDGF）上调，PDGF是HSC中的一种促有丝分裂原。COX-2负责PDGF刺激的LI90细胞中PGE2和PGI2的产生。此外，我们证明COX-2和PGE2介导了LI90对PDGF的增殖反应，而PGI2的合成类似物表现出抗增殖作用。我们的发现表明前列腺素在肝纤维化形成过程中存在复杂的相互作用。需要使用动物模型进行体内研究，以阐明非甾体抗炎药或COX-2抑制剂抑制COX-2对肝纤维化的影响。
