Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells

Authors

  • Feng Zhang,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Zili Zhang,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Li Chen,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Desong Kong,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Xiaoping Zhang,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Chunfeng Lu,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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  • Yin Lu,

    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
    2. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
    3. National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, China
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  • Shizhong Zheng

    Corresponding author
    1. Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
    2. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
    3. National First-Class Key Discipline for Traditional Chinese Medicine of Nanjing University of Chinese Medicine, Nanjing, China
    • Correspondence to: Shizhong ZHENG,

      Department of Pharmacology, College of Pharmacy,

      Nanjing University of Chinese Medicine, 138 Xianlin Avenue,

      Nanjing, Jiangsu 210023, China.

      Tel.: +86 25 86798154

      Fax: +86 25 86798188

      E-mail: nytws@163.com

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Abstract

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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