Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells.
Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells.
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姜黄素可减弱肝纤维化中的血管生成并抑制肝星状细胞的血管生成特性
DOI：
10.1111/jcmm.12286
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Zhang F;Zhang Z;Chen L;Kong D;Zhang X;Lu C;Lu Y;Zheng S
肝纤维化伴随着肝窦病理性血管生成，这已被认为是治疗慢性肝病的新治疗靶点。我们之前的研究表明姜黄素具有有效的抗纤维化活性，但其机制仍有待阐明。目前的工作表明，姜黄素可改善四氯化碳引起的大鼠肝脏纤维化损伤和肝窦血管生成。姜黄素降低了纤维化肝脏中许多血管生成标记物的表达。体外实验表明，姜黄素不会损害大鼠肝窦内皮细胞的活力和血管化以及大鼠主动脉环血管生成。这些结果表明，具有肝脏特异性周细胞特征的肝星状细胞（HSC）可能是姜黄素的潜在靶细胞。进一步的研究表明，姜黄素抑制 HSC 中 VEGF 的表达，与破坏血小板衍生生长因子-β 受体 (PDGF-βR)/ERK 和 mTOR 通路相关。姜黄素也可抑制 HSC 运动和血管形成，姜黄素与阻断 PDGF-βR/粘着斑激酶/RhoA 级联相关。功能获得或丧失分析表明，姜黄素需要激活过氧化物酶体增殖物激活受体-γ (PPAR-γ) 来抑制 HSC 的血管生成特性。我们得出的结论是，姜黄素可能通过 PPAR-γ 激活依赖性机制靶向 HSC，从而减弱肝纤维化中的肝窦血管生成。 PPAR-γ可能是减少肝纤维化过程中病理性血管生成的靶分子。
Hepatic fibrosis is concomitant with sinusoidal pathological angiogenesis, which has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. Our prior studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of a number of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells and rat aortic ring angiogenesis were not impaired by curcumin. These results indicated that hepatic stellate cells (HSCs) that are characterized as liver‐specific pericytes could be potential target cells for curcumin. Further investigations showed that curcumin inhibited VEGF expression in HSCs associated with disrupting platelet‐derived growth factor‐β receptor (PDGF‐βR)/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin associated with blocking PDGF‐βR/focal adhesion kinase/RhoA cascade. Gain‐ or loss‐of‐function analyses revealed that activation of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPAR‐γ activation‐dependent mechanism. PPAR‐γ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.
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DOI：
10.4049/jimmunol.181.1.235
发表时间：
2008-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bonfield TL;Thomassen MJ;Farver CF;Abraham S;Koloze MT;Zhang X;Mosser DM;Culver DA
通讯作者：
Culver DA
影响因子：
5
作者：
Lin, Jianguo;Chen, Anping
通讯作者：
Chen, Anping
影响因子：
15.9
作者：
Cao, Sheng;Yaqoob, Usman;Shah, Vijay H.
通讯作者：
Shah, Vijay H.
影响因子：
4.8
作者：
Karar J;Maity A
通讯作者：
Maity A
影响因子：
--
作者：
McCubrey JA;Steelman LS;Chappell WH;Abrams SL;Franklin RA;Montalto G;Cervello M;Libra M;Candido S;Malaponte G;Mazzarino MC;Fagone P;Nicoletti F;Bäsecke J;Mijatovic S;Maksimovic-Ivanic D;Milella M;Tafuri A;Chiarini F;Evangelisti C;Cocco L;Martelli AM
通讯作者：
Martelli AM