MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression.
MiR-34c promotes hepatic stellate cell activation and Liver Fibrogenesis by suppressing ACSL1 expression.
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MiR-34c 通过抑制 ACSL1 表达促进肝星状细胞活化和肝纤维形成
DOI：
10.7150/ijms.51589
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发表时间：
2021
影响因子：
3.6
通讯作者：
Yu H
中科院分区：
文献类型：
--
作者：
Li B;Liu J;Xin X;Zhang L;Zhou J;Xia C;Zhu W;Yu H
正常情况下，有多个microrna参与肝纤维化的发病机制。在我们的工作中，我们旨在确定miR-34c在肝星状细胞（HSC）活化和肝纤维化中的作用及其潜在机制。我们的研究结果表明，在HSC自然活化过程中，miR-34c水平显著升高，而影响脂肪酸（FA）合成的关键酶酰基辅酶a合成酶长链家族成员-1（ACSL1）水平降低。双荧光报告基因实验进一步证实ACSL1是miR-34c的直接靶基因。此外，抑制miR-34C可以减弱HSC-T6中胶原的合成。在我们的拯救实验中，在稳定的低表达ACSL1细胞系中，与转染miR-34c抑制剂的正常对照细胞相比，ACSL1的表达高1.49倍。α-SMA和Col1α表达量分别下降18.22%和2.58%。此外，我们使用二甲基亚硝胺（DMN）联合miR-34c agomir进行了体内模型，DMN和miR-34c agomir联合治疗可增加肝纤维化。同时，与未处理组相比，miR-34c模拟物单独处理大鼠和HSC-T6细胞的肝纤维化程度明显增加，脂滴明显减少。我们的研究结果表明，miR-34c通过靶向与脂滴密切相关的ACSL1在肝纤维化中发挥重要作用，可能作为潜在的治疗靶点。
Normally, there are multiple microRNAs involved in the pathogenesis of liver fibrosis. In our work, we aimed at identifying the role of miR-34c in the hepatic stellate cell (HSC) activation and liver fibrosis and its potential mechanism. Our results have shown that during natural activation of HSC, the level of miR-34c was increased significantly whereas acyl-CoA synthetase long-chain family member-1(ACSL1), which is a key enzyme can affect fatty acid(FA) synthesis, was decreased. A double fluorescence reporter assay further confirmed that ACSL1 is a direct target gene of miR-34c. Moreover, the inhibition of miR-34C can attenuate the synthesis of collagen in HSC-T6. In our rescue assay, ACSL1 expression was 1.49-fold higher compared to normal control cells which were transfected with the miR-34c inhibitor in a stable low expression ACSL1 cell line. While at the same time, α-SMA and Col1α expression decreased by 18.22% and 2.58%, respectively. Moreover, we performed an in vivo model using dimethylnitrosamine (DMN) in conjunction with the miR-34c agomir, combined with the treatment of DMN and the miR-34c agomir can increase liver fibrosis. Meanwhile, the degree of hepatic fibrosis was increased and lipid droplets reduced dramatically in rats and HSC-T6 cell treated with miR-34c mimics alone compared to untreated groups. Our results indicate that miR-34c plays an essential role in liver fibrosis by targeting ACSL1 closely associated with lipid droplets, and it might be used as a potential therapeutic target.
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影响因子：
5.6
作者：
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