BACKGROUND The transformation of hepatic stellate cells (HSCs) into collagen-producing myofibroblasts is a key event in hepatic fibrogenesis. Recent studies have shown that microRNAs (miRNAs) play a critical role in the transformation of HSCs. However, the function of miR-489-3p in liver fibrosis remains unclear. METHODS Here, we detected the levels of miR-489-3p and jagged canonical Notch ligand 1 (JAG1) in liver fibrosis by using CCl4-treated rats as an in vivo model and transforming growth factor-beta 1 (TGF-β1)-treated HSC cell lines LX-2 and HSC-T6 as in vitro models. The expression of profibrotic markers was affected by transfecting LX-2 cells with either miR-489-3p mimic or si-JAG1. A dual-luciferase reporter assay was carried out to study the interaction of JAG1 with miR-489-3p. RESULTS We found that miR-489-3p was remarkably decreased while JAG1 was increased in liver fibrosis models both in vivo and in vitro. Overexpression of miR-489-3p reduced the expression of profibrotic markers and the activation of LX-2 cells induced by TGF-β1. Moreover, miR-489-3p decreased the expression of jagged canonical Notch ligand 1 (JAG1) in LX-2 cells by interacting with its 3'-UTR. As JAG1 is a Notch ligand, decreased JAG1 by miR-489-3p inhibited the Notch signaling pathway. Moreover, the downregulation of JAG1 inhibited the expression of fibrotic markers. CONCLUSION Our results indicate that miR-489-3p can inhibit HSC activation by inhibiting the JAG1/Notch3 signaling pathway.

中文翻译：

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MicroRNA-489-3p通过负调控JAG1 / Notch3信号通路抑制肝星状细胞的活化。

背景技术肝星状细胞（HSC）向产生胶原的成肌纤维细胞的转化是肝纤维化中的关键事件。最近的研究表明，microRNA（miRNA）在HSC的转化中起关键作用。但是，miR-489-3p在肝纤维化中的功能仍不清楚。方法在这里，我们以CCl4处理的大鼠作为体内模型并转化生长因子β1（TGF-β1）处理，检测了肝纤维化中miR-489-3p和锯齿状典型Notch配体1（JAG1）的水平HSC细胞系LX-2和HSC-T6作为体外模型。通过用miR-489-3p模仿物或si-JAG1转染LX-2细胞可以影响纤维化标志物的表达。进行了双重荧光素酶报告基因测定，以研究JAG1与miR-489-3p的相互作用。结果我们发现在体内和体外肝纤维化模型中，miR-489-3p显着降低而JAG1升高。miR-489-3p的过表达降低了TGF-β1诱导的纤维化标志物的表达和LX-2细胞的活化。此外，miR-489-3p通过与其3'-UTR相互作用，降低了LX-2细胞中锯齿状Notch配体1（JAG1）的表达。由于JAG1是Notch配体，miR-489-3p降低JAG1会抑制Notch信号通路。此外，JAG1的下调抑制了纤维化标记物的表达。结论我们的结果表明，miR-489-3p可以通过抑制JAG1 / Notch3信号通路来抑制HSC活化。miR-489-3p的过表达降低了TGF-β1诱导的纤维化标志物的表达和LX-2细胞的活化。此外，miR-489-3p通过与其3'-UTR相互作用，降低了LX-2细胞中锯齿状Notch配体1（JAG1）的表达。由于JAG1是Notch配体，miR-489-3p降低JAG1会抑制Notch信号通路。此外，JAG1的下调抑制了纤维化标记物的表达。结论我们的结果表明，miR-489-3p可以通过抑制JAG1 / Notch3信号通路来抑制HSC活化。miR-489-3p的过表达降低了TGF-β1诱导的纤维化标志物的表达和LX-2细胞的活化。此外，miR-489-3p通过与其3'-UTR相互作用，降低了LX-2细胞中锯齿状Notch配体1（JAG1）的表达。由于JAG1是Notch配体，miR-489-3p降低JAG1会抑制Notch信号通路。此外，JAG1的下调抑制了纤维化标志物的表达。结论我们的结果表明，miR-489-3p可以通过抑制JAG1 / Notch3信号通路来抑制HSC活化。JAG1的下调抑制了纤维化标志物的表达。结论我们的结果表明，miR-489-3p可以通过抑制JAG1 / Notch3信号通路来抑制HSC活化。JAG1的下调抑制了纤维化标志物的表达。结论我们的结果表明，miR-489-3p可以通过抑制JAG1 / Notch3信号通路来抑制HSC活化。