Over-expression of C/EBP-alpha induces apoptosis in cultured rat hepatic stellate cells depending on p53 and peroxisome proliferator-activated receptor-gamma.
Hepatic stellate cells (HSCs) play a key role in the pathogenesis of hepatic fibrosis. In our previous studies, CCAAT enhancer binding protein-alpha (C/EBP-alpha) has been shown to be involved in the activation of HSCs and to have a repression effect on hepatic fibrosis in vivo. However, the mechanisms are largely unknown. In this study, we show that the infection of adenovirus vector expressing C/EBP-alpha gene (Ad-C/EBP-alpha) could induce HSCs apoptosis in a dose- and time-dependent manner by Annexin V/PI staining, caspase-3 activation assay, and flow cytometry. Also, over-expression of C/EBP-alpha resulted in the up-regulation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and P53, while P53 expression was regulated by PPAR-gamma. In addition, Fas, FasL, DR4, DR5, and TRAIL were studied. The results indicated that the death receptor pathway was mainly involved and regulated by PPAR-gamma and p53 in the process of apoptosis triggered by C/EBP-alpha in HSCs.
Wang
Xueqing
X
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yi Xue Yuan Road, Shanghai 200032, PR China.
Huang
Guangcun
G
Mei
Shuang
S
Qian
Jin
J
Ji
Juling
J
Zhang
Jinsheng
J
D000818:Animals; D017209:Apoptosis; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis* / Q000235:genetics; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D008099:Liver / Q000166:cytology / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D053218:Receptors, Death Domain / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D061945:Caspase Inhibitors; D047495:PPAR gamma; D053218:Receptors, Death Domain; D016159:Tumor Suppressor Protein p53; D053181:Caspase 8; D053453:Caspase 9