MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4
MicroRNA-146b regulates hepatic stellate cell activation via targeting of KLF4
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DOI：
10.5604/16652681.1222111
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发表时间：
2016-11-01
影响因子：
3.8
通讯作者：
Xiang, Tianxing
中科院分区：
文献类型：
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作者：
Ge, Shanfei;Zhang, Lunli;Xiang, Tianxing
背景我们先前通过深度测序技术和基因表达分析确定miR-146 b上调了肝纤维化的发生。然而，miR 146 b在肝星状细胞（HSC）中的作用和相关机制尚未阐明，所述肝星状细胞参与纤维化和纤维化。结果我们报道了在TGF-β 1处理的HSC中miR-146 b的表达增加。与转染抑制剂NC的细胞相比，TGF-β 1增强了这些细胞的α-SMA和COL 1A 1蛋白表达。相反，miR-146 b敲低降低了α-SMA和COL 1A 1表达并抑制了HSC增殖。此外，我们发现miR-146 b通过靶向其3'非翻译区特异性地调节kruppel样因子4（KLF 4）的翻译。KLF 4的强制表达抑制了TGF-β 1诱导的HSC中α-SMA和COL 1A 1表达的增强，以及这些细胞的增殖。在肝纤维化过程中，miR-146 b的表达与KLF 4的表达呈负相关，与α-SMA和COL 1A 1的表达呈正相关。结论。我们的研究结果表明miR-146 b通过直接靶向KLF 4作为HSC活化的新型上游效应的参与。因此，将miR-146 b靶向转移到HSC中可能是治疗肝纤维化的有用策略。
Background. We previously identified miR-146b as being up regulated thedevelopment of hepatic fibrosis using deep sequencing technology and gene expression analysis. However, the roles and related mechanisms of miR146b 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-beta 1-treated HSCs. TGF-beta 1 enhanced a-SMA and COL1A1 protin expression eration of these cells compared with cells transfected with inhibitor NC. Conversely, miR-146b knock-down decreased alpha-SMA and COL1A1 expression and inhibited HSC proliferation. in addition we found that miR-146b specifically regulated the translation of kruppel-liked factor 4 (KLF4) by targeting its 3' untranslated region. Forced expression of KLF4 nhibited TGF-beta 1-induced enhancement of alpha-SMA and COL1A1 expression in HSCs, as well as proliferation of these cells. More over, miR-146b expresssion was negatively associated with KLF4 expression but positively associated with expression of alpha-SMA and COL1A1 during hepatic fibrosis. Conculusions. Our findings demonstrate the participation of miR-146b as a novel upstream effect 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.