MicroRNA-489-3p Represses Hepatic Stellate Cells Activation by Negatively Regulating the JAG1/Notch3 Signaling Pathway.
Dig Dis Sci
; 66(1): 143-150, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-32144602
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-ß1)-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-ß1. 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
MicroRNAs
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Hepatic Stellate Cells
/
Jagged-1 Protein
/
Receptor, Notch3
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Liver Cirrhosis
Type of study:
Prognostic_studies
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Dig Dis Sci
Year:
2021
Document type:
Article
Affiliation country:
China