Department of Gastroenterology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Department of Biochemistry & Molecular Biology, Medical College, Nantong University, Qi Xiou Road 19, Nantong 226001, Jiangsu, China.
Eur J Pharmacol. 2014 Apr 5;728:9-15. doi: 10.1016/j.ejphar.2014.01.074. Epub 2014 Feb 15.
Hepatic stellate cell activation is a key cellular event in the development of liver fibrosis. Recently, Delta-like homolog 1 (DLK1) protein level has been shown to increase in HSC activation and serve as a new contributor to HSC activation and liver fibrosis. Curcumin, a natural yellow polyphenol, possesses therapeutic roles in many diseases including liver fibrosis and has long been used in traditional medicine. The present study was aimed to elucidate the effect of curcumin on DLK1 expression in HSCs in vitro and in vivo, which is still unknown. Our results demonstrated that curcumin reduced DLK1 expression in culture-activated HSCs and in rat model of liver fibrosis. The inhibitory effect of curcumin on DLK1 expression may be mediated in part by interruption of Shh signaling pathway, which contributes to the promotion effect of curcumin on the expression of PPAR-gamma, a key factor in inhibiting HSC activation. Our results in this study may reveal a new mechanisms through which curcumin exerts its inhibitory effect on HSC activation and liver fibrosis.
肝星状细胞激活是肝纤维化发展的关键细胞事件。最近，Delta-like 同源物 1（DLK1）蛋白水平在 HSC 激活中增加，并作为 HSC 激活和肝纤维化的新贡献者。姜黄素是一种天然的黄色多酚，具有多种疾病的治疗作用，包括肝纤维化，并在传统医学中长期使用。本研究旨在阐明姜黄素对体外和体内 HSCs 中 DLK1 表达的影响，这在以前是未知的。我们的结果表明，姜黄素降低了培养激活的 HSCs 和肝纤维化大鼠模型中的 DLK1 表达。姜黄素对 DLK1 表达的抑制作用可能部分通过中断 Shh 信号通路介导，这有助于促进姜黄素对 PPAR-γ的表达，PPAR-γ是抑制 HSC 激活的关键因素。我们在这项研究中的结果可能揭示了姜黄素抑制 HSC 激活和肝纤维化的新机制。
