The activation of hepatic stellate cells(HSCs)is a major event during hepatic fibrogenesis.Restoration of intracellular lipid droplet(LD)formation turns the activated HSC back to a quiescent state.Our previous studies...The activation of hepatic stellate cells(HSCs)is a major event during hepatic fibrogenesis.Restoration of intracellular lipid droplet(LD)formation turns the activated HSC back to a quiescent state.Our previous studies have shown that curcumin suppresses HSC activation through increasing peroxisome proliferator-activated receptor,gamma(PPARγ)and 5′adenosine monophosphate-activated protein kinase(AMPK)activities.This study aims at evaluating the effect of curcumin on lipid accumulation in HSCs and hepatocytes,and further elucidating the underlying mechanisms.Now we showed that curcumin increased LD formation in activated HSCs and stimulated the expression of sterol regulatory element-binding protein and fatty acid synthase,and reduced the expression of adipose triglyceride lipase.Exogenous perilin5 expression in primary HSCs promoted LD formation.Perilipin 5 siRNA eliminated curcumin-induced LD formation in HSCs.These results suggest that curcumin recovers LD formation and lipid accumulation in activated HSCs by increasing perilipin 5 gene expression.Furthermore,inhibition of AMPK or PPARy activity blocked curcumin's effect on Plin5 gene expression and LD formation.Our results provide a novel evidence in vitro for curcumin as a safe,effective candidate to treat liver fibrosis.展开更多
基金This study was supported by the National Natural Science Foundation of China(No.81760356)to Dr.Xiao-qun HAN and Talent Initial Funding(No.YY2017-002)sponsored by Guangdong Second Provincial General Hospital to Jian-guo LINsponsored by Medical Scientific and Technological Research Program of Guangdong Province(No.C2019056)to Jian-guo LIN.
文摘The activation of hepatic stellate cells(HSCs)is a major event during hepatic fibrogenesis.Restoration of intracellular lipid droplet(LD)formation turns the activated HSC back to a quiescent state.Our previous studies have shown that curcumin suppresses HSC activation through increasing peroxisome proliferator-activated receptor,gamma(PPARγ)and 5′adenosine monophosphate-activated protein kinase(AMPK)activities.This study aims at evaluating the effect of curcumin on lipid accumulation in HSCs and hepatocytes,and further elucidating the underlying mechanisms.Now we showed that curcumin increased LD formation in activated HSCs and stimulated the expression of sterol regulatory element-binding protein and fatty acid synthase,and reduced the expression of adipose triglyceride lipase.Exogenous perilin5 expression in primary HSCs promoted LD formation.Perilipin 5 siRNA eliminated curcumin-induced LD formation in HSCs.These results suggest that curcumin recovers LD formation and lipid accumulation in activated HSCs by increasing perilipin 5 gene expression.Furthermore,inhibition of AMPK or PPARy activity blocked curcumin's effect on Plin5 gene expression and LD formation.Our results provide a novel evidence in vitro for curcumin as a safe,effective candidate to treat liver fibrosis.
