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

Journal of Cellular and Molecular Medicine

Feng Zhang¹  Zili Zhang¹  Li Chen¹  Desong Kong¹  Xiaoping Zhang¹  Chunfeng Lu¹  Yin Lu¹ 

[1] Department of Pharmacology, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China

关键词: liver fibrosis;    angiogenesis;    hepatic stellate cell;    curcumin;    peroxisome proliferator‐activated receptor‐γ;    VEGF;   

DOI  :  10.1111/jcmm.12286

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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