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07.03.2020 | Original Article

MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway

verfasst von: Juanjuan Li, Shouquan Dong, Mingliang Ye, Ganjing Peng, Jie Luo, Chun Wang, Jing Wang, Qiu Zhao, Ying Chang, Hongling Wang

Erschienen in: Digestive Diseases and Sciences | Ausgabe 1/2021

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Abstract

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 3ʹ-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.

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Titel: MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway
verfasst von: Juanjuan Li
Shouquan Dong
Mingliang Ye
Ganjing Peng
Jie Luo
Chun Wang
Jing Wang
Qiu Zhao
Ying Chang
Hongling Wang
Publikationsdatum: 07.03.2020
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 1/2021
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-020-06174-w

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MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway