Ferulic acid suppresses activation of hepatic stellate cells through ERK1/2 and Smad signaling pathways in vitro
Ferulic acid suppresses activation of hepatic stellate cells through ERK1/2 and Smad signaling pathways in vitro
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阿魏酸在体外通过 ERK1/2 和 Smad 信号通路抑制肝星状细胞的活化
DOI：
10.1016/j.bcp.2014.10.016
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发表时间：
2015-01-01
影响因子：
5.8
通讯作者：
Niu, Yingcai
中科院分区：
文献类型：
--
作者：
Xu, Tianjiao;Pan, Zhi;Niu, Yingcai
肝星状细胞（HSC）是肝纤维化基质成分的主要来源。阿魏酸（FA）在肾脏和心脏疾病中具有抗纤维化潜力。然而，FA是否包含HSC活化的抑制作用仍有待澄清。本研究旨在评估FA通过阻断HSC-T6细胞外信号调节激酶I和2（ERK 1/2）或/和Smad信号通路抑制细胞外基质（ECM）相关基因表达的假设。我们的结果表明，FA显着抑制HSC-T6细胞在体外的活力和激活。此外，我们证明，第一次，FA显着抑制α 1（I）胶原蛋白（Col-I）和纤连蛋白在转录和翻译水平的表达。此外，FA治疗抑制Smad转录活性，通过瞬时转染含有SMAD反应元件和荧光素酶报告基因的质粒构建进行评估。FA对HSC活化的抑制作用以独立的方式参与了粘着斑激酶（FAK）依赖的ERK 1/2和Smad信号通路。通过中和抗体阻断转化生长因子-β导致ERK 1/2和Smad信号传导显著减少。这些结果支持FA作为预防和治疗肝纤维化的有效治疗剂。(C)2014 Elsevier Inc. All rights reserved.
Hepatic stellate cells (HSCs) are the primary source of matrix components in hepatic fibrosis. Ferulic acid (FA) has antifibrotic potential in renal and cardiac disease. However, whether FA comprises inhibitive effects of HSCs activation remains to be clarified. This study aims at evaluating the hypothesis that FA inhibits extracellular matrix (ECM)-related gene expression by the interruption of the extracellular signal-regulated kinases I and 2 (ERK1/2) or/and Smad signaling pathways in HSC-T6. Our results indicated that FA significantly inhibited both viability and activation of HSC-T6 cells in vitro. In addition, we demonstrated, for the first time, that FA dramatically inhibited the expression of alpha 1 (I) collagen (Col-I) and fibronectin at levels of transcription and translation. Moreover, FA treatment inhibited Smad transcriptional activity, as evaluated by transient transfection with a plasmid construction containing SMAD response element and the luciferase reporter gene. Furthermore, FA inhibition of HSCs activation involved in both focal adhesion kinase (FAK)-dependent ERK1/2 and Smad signaling pathways with independent manner. Blocking transforming growth factor-beta by a neutralizing antibody caused a marked reduction in both ERK1/2 and Smad signaling. These results support FA as an effective therapeutic agent for the prevention and treatment of hepatic fibrosis. (C) 2014 Elsevier Inc. All rights reserved.