Curcumin regulates delta-like homolog 1 expression in activated hepatic stellate cell

Eur J Pharmacol. 2014 Apr 5:728:9-15. doi: 10.1016/j.ejphar.2014.01.074. Epub 2014 Feb 15.

Abstract

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.

Keywords: Curcumin; Delta-like homolog 1; Hepatic stellate cell; Liver fibrosis; Sonic Hedgehog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Blotting, Western
  • Cells, Cultured
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Curcumin / therapeutic use
  • Disease Models, Animal
  • Gene Expression / drug effects*
  • Hepatic Stellate Cells / drug effects*
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Membrane Proteins / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Thioacetamide / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Dlk1 protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Thioacetamide
  • Curcumin