Nrf2 activation is required for curcumin to induce lipocyte phenotype in hepatic stellate cells.

Abstract

Hepatic fibrosis is a reversible scarring response that commonly occurs with chronic liver injury. During hepatic fibrogenesis, the major effector hepatic stellate cells (HSCs) become activated, featured by disappeared intracellular lipid droplets, decreased retinoid storage, and dysregulated expression of genes associated with lipid and retinoid metabolism. Compelling evidence suggested that recovery of retinoid droplets could inhibit HSC activation, while the precise molecular basis underlying the phenotypical switch still remained unclear. In this study, curcumin increased the abundance of lipid droplets and content of triglyceride in activated HSCs. In addition, curcumin could concentration-dependently regulate genes associated with lipid and retinoid metabolism. Further, consistent results were obtained from in vivo experiments. Curcumin increased Nrf2 expression and nuclear translocation, and its binding activity to DNA, which might be associated with suppression of Kelch-like ECH-associated protein 1 in HSCs. Of interest was that Nrf2 overexpression plasmids, in contract to Nrf2 siRNA, strengthened the effect of curcumin on induction of lipocyte phenotype. In in vivo system, Nrf2 knockdown mediated by Nrf2 shRNA lentivirus not only accelerated the lipid degradation in HSCs but also promoted the progression of CCl4-induced hepatic fibrosis in mice. Noteworthily, Nrf2 knockdown abolished the protective effect of curcumin. In conclusion, curcumin could induce lipocyte phenotype of activated HSCs via activating Nrf2. Nrf2 could be a target molecule for antifibrotic strategy.

DOI: 10.1016/j.biopha.2017.08.037

Cite this paper

@article{Lu2017Nrf2AI, title={Nrf2 activation is required for curcumin to induce lipocyte phenotype in hepatic stellate cells.}, author={Chunfeng Lu and Wenxuan Xu and Shizhong Zheng}, journal={Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, year={2017}, volume={95}, pages={1-10} }