DLPC and SAMe prevent alpha1(I) collagen mRNA up-regulation in human hepatic stellate cells, whether caused by leptin or menadione.

DLPC and SAMe prevent alpha1(I) collagen mRNA up-regulation in human hepatic stellate cells, whether caused by leptin or menadione.
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DLPC 和 SAMe 可防止人肝星状细胞中 α1(I) 胶原蛋白 mRNA 的上调,无论是由瘦素还是甲萘醌引起的。

DOI:
10.1016/j.bbrc.2006.08.174
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发表时间:
2006
影响因子:
3.1
通讯作者:
Lieber,CharlesS
Lieber,CharlesS
中科院分区:
生物学4区
文献类型:
--
作者:
Cao,Qi;Mak,KiM;Lieber,CharlesS

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我们以前报道,二亚油酰磷脂酰胆碱(DLPC)和S-腺苷甲硫氨酸(SAMe)的组合,这具有抗氧化特性和抗纤维化的行动,阻止瘦素刺激的金属蛋白酶组织抑制剂(TIMP)-1的生产在肝星状细胞(HSC)通过抑制过氧化氢介导的信号转导。我们现在发现DLPC和SAMe抑制LX-2人HSC中瘦素或甲萘醌诱导的α1(I)胶原mRNA表达。我们发现,DLPC和SAMe防止H2 O2的产生和恢复还原型谷胱甘肽(GSH)的消耗是否引起的瘦素或甲萘醌。通过ERK 1/2和p38通路阻断H2 O2信号通路,可完全抑制瘦素或甲萘醌诱导的α1(I)胶原mRNA表达。DLPC和SAMe联合应用对胶原mRNA的抑制作用比单独应用DLPC或SAMe至少高2倍。与TIMP-1产生的预防相结合,DLPC和SAMe抑制α1(I)胶原mRNA表达的能力为这些无害化合物预防肝纤维化提供了机制基础,因为TIMP-1和胶原产生的增强与肝纤维化发生相关,并且它们的减弱可以减少纤维化。
We previously reported that the combination of dilinoleoylphosphatidylcholine (DLPC) and S-adenosylmethionine (SAMe), which have antioxidant properties and antifibrogenic actions, prevented leptin-stimulated tissue inhibitor of metalloproteinase (TIMP)-1 production in hepatic stellate cells (HSCs) by inhibiting H2O2-mediated signal transduction. We now show that DLPC and SAMe inhibit α1(I) collagen mRNA expression induced by leptin or menadione in LX-2 human HSCs. We found that DLPC and SAMe prevent H2O2generation and restore reduced glutathione (GSH) depletion whether caused by leptin or menadione. Blocking H2O2signaling through ERK1/2 and p38 pathways resulted in a complete inhibition of leptin or menadione-induced α1(I) collagen mRNA. The inhibition of collagen mRNA by DLPC and SAMe combined is at least two times more effective than that by DLPC or SAMe alone. In conjunction with the prevention of TIMP-1 production, the ability of DLPC and SAMe to inhibit α1(I) collagen mRNA expression provides a mechanistic basis for these innocuous compounds in the prevention of hepatic fibrosis, because enhanced TIMP-1 and collagen productions are associated with hepatic fibrogenesis and their attenuation may diminish fibrosis.
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