Involvement of C/EBP-alpha gene in in vitro activation of rat hepatic stellate cells.
Hepatic stellate cells (HSCs) play key roles in hepatic fibrosis. One of the most striking alterations in activated HSCs is loss of cytoplasmic lipid droplets. However, the association of lipid storage with the activation of HSCs remains unclear. CCAAT/enhancer-binding proteins family (C/EBPs), especially C/EBP-alpha, controls differentiation of adipocytes. We suggested that C/EBP-alpha gene may be involved in HSCs activation. The present results showed that the expression levels of C/EBP-alpha and C/EBP-beta genes declined in activated HSCs. Over-expression of C/EBP-alpha gene in activated HSCs: (1) inhibited HSCs proliferation, extracellular matrix-producing, alpha-smooth muscle actin gene expression, and induced rebound of cytoplasmic lipid droplets; (2) reduced retinoic acid receptor-beta, C/EBP-delta and -beta gene expressions, but increased the active form C/EBP-beta PSer(105), and induced retinoid X receptor-alpha gene expression; and (3) did not affect the protein level of p16INK4a, p21Cip1/WAF1 or p27Kip1. In conclusions, C/EBP-alpha gene is involved in in vitro activation of rat HSCs.
Huang
Guang-Cun
GC
Department of Pathology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
Zhang
Jin-Sheng
JS
Tang
Qi-Qun
QQ
D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D018797:Cell Cycle Proteins; D018168:Receptors, Retinoic Acid; D018844:Cyclin-Dependent Kinases