Resumen

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-â1-treated HSCs. TGF-â1 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 áSMA 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-á1-induced enhancement of áSMA 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 áSMA 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.

Palabras clave: miR-146b KLF4 hepatic stellate cell fibrosis.

2016-11-18   |   446 visitas   |   Evalua este artículo 0 valoraciones

Vol. 15 Núm.6. Noviembre-Diciembre 2016 Pags. 918-928 Ann Hepatol 2016; 15(6)