MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4



Document title: MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4
Journal: Annals of hepatology
Database: PERIÓDICA
System number: 000406043
ISSN: 1665-2681
Authors: 1
1
2
2
3
3

1
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:
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
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