C/EBP-α ameliorates CCl(4)-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo

• Published in: Apoptosis (London) 2012-05, Vol.17 (5), p.492
• Main Authors: Tao, Li-Li, Cheng, Yuan-Yuan, Ding, Di, Mei, Shuang, Xu, Jia-Wen, Yu, Juan, Ou-Yang, Qi, Deng, Long, Chen, Qi, Li, Qing-Quan, Xu, Zu-De, Liu, Xiu-Ping
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Apoptosis; Carbon Tetrachloride; Caspases - genetics; Caspases - metabolism; CCAAT-Enhancer-Binding Protein-alpha - biosynthesis; CCAAT-Enhancer-Binding Protein-alpha - genetics; CCAAT-Enhancer-Binding Protein-alpha - physiology; Cells, Cultured; Collagen - metabolism; DNA Fragmentation; Extracellular Matrix - metabolism; gamma-Glutamyltransferase - metabolism; Gene Expression; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - physiology; Hepatocytes - metabolism; Hepatocytes - physiology; Hydroxyproline - metabolism; Liver Cirrhosis - chemically induced; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; Male; Mice; Mice, Inbred BALB C; Rats; Recombinant Proteins - biosynthesis; Recombinant Proteins - genetics
• ISSN: 1573-675X
• DOI: 10.1007/s10495-012-0700-y

CCAAT enhancer binding protein-α (C/EBP-α) is a transcript factor that regulates adipocyte differentiation and induces apoptosis in hepatic stellate cells (HSCs) in vivo and in vitro. However, the effect of C/EBP-α on hepatocytes in vivo remains unknown. This study investigated whether C/EBP-α exerts different apoptotic effects on hepatocytes and HSCs in vitro and in vivo. An adenovirus vector-expressing C/EBP-α gene was constructed, and a rat hepatic stellate cell lines (HSC-T6) and hepatocytes were transfected. A CCl(4)-induced liver fibrosis model in mice was also utilized. C/EBP-α induced apoptosis in hepatocytes and HSCs, but a significant difference between these cell types was observed in vitro. The mitochondrial pathway was involved in the apoptotic process and was predominant in HSC-T6 apoptosis. In the CCl(4)-induced mice liver fibrosis model, the administration of Ad-C/EBP-α decreased extracellular matrix deposition, including collagen and hydroxyproline content, and γ-GT levels, a marker of liver damage, were reduced significantly. Immunohistochemistry and TUNEL assay results showed an increase of apoptosis in HSCs, but hepatocytes were less affected. C/EBP-α induced differential apoptotic effects in hepatocytes and HSCs in vitro and in vivo. This differential effect could be a potential target for the treatment of hepatic fibrosis with little hepatic toxicity.