Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation.
Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation.
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姜黄素通过抑制胆管细胞炎症反应和门户肌纤维细胞增殖来改善MDR2 - / - 小鼠中的硬化性胆管炎。
DOI：
10.1136/gut.2009.186528
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发表时间：
2010-04
期刊：
影响因子：
24.5
通讯作者：
Trauner M
中科院分区：
文献类型：
--
作者：
Baghdasaryan A;Claudel T;Kosters A;Gumhold J;Silbert D;Thüringer A;Leski K;Fickert P;Karpen SJ;Trauner M
慢性胆管病的治疗选择有限，是肝移植的重要指征。姜黄素是香料姜黄的黄色色素，具有多效性，可减轻化学性肝损伤动物模型的肝损伤。姜黄素对胆管疾病是否有有益作用尚不清楚。姜黄素作为慢性胆管病小鼠模型，在Mdr2 - / -小鼠体内探讨了其潜在的抗淤胆、抗炎和抗纤维化机制；以及在体外从Mdr2 - / -小鼠分离的胆管细胞细胞系（HuCCT1）和门脉肌成纤维细胞（MFBs）。姜黄素喂养后，Mdr2 - / -小鼠的肝损伤、胆汁淤积和纤维化减轻。此外，姜黄素抑制Mdr2−/−小鼠胆管细胞增殖和激活标记物血管细胞粘附分子-1 （VCAM-1）的表达。姜黄素——类似于PPARγ合成激动剂曲格列酮——在体外直接抑制TNF-α诱导的胆管细胞炎症激活，而姜黄素的这些有益作用在很大程度上被PPARγ合成拮抗剂阻断。此外，姜黄素通过抑制ERK1/2磷酸化抑制门静脉mfb的增殖和激活，从而减少纤维形成。这些结果表明，姜黄素可能在肝脏中具有多个靶点，包括激活胆管细胞中的PPARγ和抑制MFBs中的ERK1/2信号传导，从而调节小鼠胆管病模型中的几个中心细胞事件。靶向这些途径可能是治疗胆管疾病的一种有希望的方法。
Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. Curcumin, the yellow pigment of the spice turmeric, has pleiotropic actions and attenuates hepatic damage in animal models of chemically-induced liver injury. Whether curcumin has beneficial effects in cholangiopathies is unknown. Potential anti-cholestatic, anti-inflammatory and anti-fibrotic mechanisms of curcumin were explored in vivo in Mdr2−/− mice as a murine model of chronic cholangiopathy; as well as in vitro in a cholangiocyte cell line (HuCCT1) and portal myofibroblasts (MFBs) isolated from Mdr2−/− mice. Liver damage, cholestasis and fibrosis were reduced in Mdr2−/− mice after curcumin feeding. Moreover, curcumin inhibited cholangiocyte proliferation and expression of activation marker Vascular Cell Adhesion Molecule-1 (VCAM-1) in Mdr2−/− mice. Curcumin - similar to PPARγ synthetic agonist troglitazone - directly inhibited TNF-α induced inflammatory activation of cholangiocytes in vitro, whereas these beneficial effects of curcumin were largely blocked by a PPARγ synthetic antagonist. In addition, curcumin blocked proliferation and activation of portal MFBs by inhibiting ERK1/2 phosphorylation, thus contributing to reduced fibrogenesis. These results show that curcumin may have multiple targets in liver including activation of PPARγ in cholangiocytes and inhibition of ERK1/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.
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影响因子：
2.9
作者：
JAMALL, IS;FINELLI, VN;HEE, SSQ
通讯作者：
HEE, SSQ
影响因子：
7.3
作者：
Chen, A.;Zheng, S.
通讯作者：
Zheng, S.
DOI：
10.1186/1476-5926-2-s1-s7
发表时间：
2004-01-14
期刊：
Comparative hepatology
影响因子：
--
作者：
Hazra S;Miyahara T;Rippe RA;Tsukamoto H
通讯作者：
Tsukamoto H
影响因子：
25.7
作者：
Cullen, Susan N.;Rust, Christian;Chapman, Roger W.
通讯作者：
Chapman, Roger W.
影响因子：
2.7
作者：
Deters, M;Siegers, C;H채nsel, W
通讯作者：
H채nsel, W