Ji Juling, Zhang Jinsheng, Huang Guangcun, Qian Jin, Wang Xueqing, Mei Shuang
Department of Pathology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
FEBS Lett. 2009 Feb 18;583(4):759-66. doi: 10.1016/j.febslet.2009.01.034. Epub 2009 Jan 29.
Hepatic stellate cells (HSCs) activation is an initial event in liver fibrosis. MicroRNAs (miRNAs) have been found to play essential roles in cell differentiation, proliferation, and fat metabolism. In this study, we showed that down-regulation of two over-expressed miRNAs, miR-27a and 27b allowed culture-activated rat HSCs to switch to a more quiescent HSC phenotype, with restored cytoplasmic lipid droplets and decreased cell proliferation. Mechanistically, retinoid X receptor alpha was confirmed to be the target of miR-27a and 27b. These results indicated a new role and mechanism of miR-27a and 27b in regulating fat metabolism and cell proliferation during HSCs activation.
肝星状细胞(HSCs)激活是肝纤维化的起始事件。微小RNA(miRNAs)已被发现参与细胞分化、增殖及脂肪代谢过程。在本研究中,我们发现,两个过表达的miRNA,miR-27a与miR-27b的下调,可使培养激活的大鼠肝星状细胞转变为更静止的肝星状细胞表型,有恢复的细胞质脂滴且细胞增殖减少。机制上,维甲酸X受体α被确认为miR-27a与miR-27b的靶点。这些结果表明了miR-27a与miR-27b在肝星状细胞激活过程中调节脂肪代谢及细胞增殖的新作用及机制。