Prostaglandin E2 inhibits transforming growth factor β1-mediated induction of collagen α1(I) in hepatic stellate cells
Prostaglandin E2 inhibits transforming growth factor β1-mediated induction of collagen α1(I) in hepatic stellate cells
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DOI：
10.1016/j.jhep.2004.04.033
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发表时间：
2004-08-01
影响因子：
25.7
通讯作者：
Friedman, SL
中科院分区：
文献类型：
--
作者：
Hui, AY;Dannenberg, AJ;Friedman, SL
背景/目的：环氧化酶-2 （COX-2）与许多肝星状细胞（HSC）功能有关，但其与转化生长因子- β 1 （tgf - β 1）介导的纤维化的关系尚不清楚。我们评估了COX-2抑制和PGE(2)对永生化人HSC系LX-1中tgf - β 1刺激的基质合成的调节的影响，并在原代星状细胞中证实了这些发现。方法：采用Western blotting和实时定量PCR检测COX-2的表达。通过测定胶原α 1(I) mRNA水平，研究了选择性COX-2抑制剂NS398和PGE(2)对tgf - β - 1介导的纤维形成的影响。RT-PCR检测PGE(2)受体的表达。结果：在基础条件下，NS398抑制PGE(2)合成，诱导α 1(1)胶原，而外源PGE(2)抑制α 1(1)胶原的表达。tgf - β 1诱导COX-2 mRNA、COX-2蛋白和PGE(2)生物合成。重要的是，tgf - β - 1介导的胶原α 1(l)的诱导被外源性PGE的添加显著抑制(2)。四种主要的PGE(2)受体均在LX-1细胞中表达。结论：这些结果表明cox -2衍生的PGE(2)抑制基础和tgf - β 1介导的HSC诱导的胶原合成。基于这些发现，确定抑制cox衍生的PGE(2)合成是否会改变体内肝纤维化的进展将是重要的。(C) 2004年欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: Cyclooxygenase-2 (COX-2) has been implicated in a number of hepatic stellate cell (HSC) functions but its relationship to transforming growth factor-beta1 (TGF-beta1)-mediated fibrogenesis is unknown. We assessed the impact of COX-2 inhibition and PGE(2) on the regulation of TGF-beta1-stimulated matrix synthesis in an immortalized human HSC line, LX-1 and corroborated these findings in primary stellate cells.Methods: Expression of COX-2 was assessed by Western blotting and real time quantitative PCR. The effect of NS398, a selective COX-2 inhibitor, and PGE(2) On TGF-beta1-mediated fibrogenesis was examined by measuring mRNA levels of collagen alpha1(I). PGE(2) receptor expression was analyzed by RT-PCR.Results: Under basal conditions, NS398 suppressed PGE(2) synthesis and induced collagen alpha1(l) whereas exogenous PGE(2) suppressed expression of collagen alpha1(I). TGF-beta1 induced COX-2 mRNA, COX-2 protein and PGE(2) biosynthesis. Importantly, TGF-beta1-mediated induction of collagen alpha1(l) was markedly suppressed by the addition of exogenous PGE(2). All four major PGE(2) receptors were expressed in LX-1 cells.Conclusions: These results suggest that COX-2-derived PGE(2) inhibits both basal and TGF-beta1-mediated induction of collagen synthesis by HSC. Based on these findings, it will be important to determine whether inhibiting COX-derived PGE(2) synthesis alters the progression of liver fibrosis in vivo. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.