Ge S, Zhang L, Xie J, Liu F, He J, He J, Wang X, Xiang T

Language: English
References: 47
Page: 918-928
PDF size: 2824.49 Kb.

ABSTRACT

Background. 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. 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 hepatic fibrosis.

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