Journal: | Annals of hepatology |
Database: | PERIÓDICA |
System number: | 000406043 |
ISSN: | 1665-2681 |
Authors: | Ge, Shanfei1 Zhang, Lunli1 Xie, Jianping2 Liu, Fei2 He, Jinni3 He, Jinwen3 Wang, Xiaowei Xiang, Tianxing1 |
Institutions: | 1Nanchang University, The First Affiliated Hospital, Nanchang, Jiangxi. China 2Central South University, Xiangya Hospital, Changsha, Hunan. China 3Central South University, Xiangya School of Medicine, Changsha, Hunan. China |
Year: | 2016 |
Season: | Nov-Dic |
Volumen: | 15 |
Number: | 6 |
Pages: | 918-928 |
Country: | México |
Language: | Inglés |
Document type: | Artículo |
Approach: | Analítico, descriptivo |
English abstract | We previously identified miR-146b as being up-regulated during the development of hepatic fibrosis using deep sequencing technology and gene expression analysis. However, the roles and related mechanisms of miR-146b in hepatic stellate cells (HSCs), which are involved in fibrogenesis and fibrosis, have not been elucidated. Results. Results. We report that miR-146b expression was increased in TGF-β1-treated HSCs. TGF-β1 enhanced a-SMA and COL1A1 protein expression in HSCs and stimulated proliferation of these cells compared with cells transfected with inhibitor NC. Conversely, miR-146b knock-down decreased α-SMA and COL1A1 expression and inhibited HSC proliferation. In addition, we found that miR-146b specifically regulated the translation of Krüppel-like factor 4 (KLF4) by targeting its 3' untranslated region. Forced expression of KLF4 inhibited TGF-β1-induced enhancement of α-SMA and COL1A1 expression in HSCs, as well as proliferation of these cells. Moreover, miR-146b expression was negatively associated with KLF4 expression but positively associated with expression of α-SMA and COL1A1 during hepatic fibrosis. Conclusions. Our findings demonstrate the participation of miR-146b as a novel upstream effector of HSC activation via direct targeting of KLF4. Thus, targeted transfer of miR-146b into HSCs could be a useful strategy for the treatment of hepaticfibrosis |
Disciplines: | Medicina |
Keyword: | Gastroenterología, Genética, Fibrosis hepática, Activación celular, Regulación genética, Células estelares hepáticas |
Keyword: | Medicine, Gastroenterology, Genetics, Liver fibrosis, Cell activation, Genetic regulation, Hepatic stellate cells |
Full text: | Texto completo (Ver PDF) |