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image of miRNA-29b-3p: An Important Target for Ameliorating Liver Fibrosis in Wilson Disease by Inhibiting Autophagy

Abstract

Background

Liver fibrosis is an important pathological feature of Wilson disease (WD). The miRNA-29b-3p level decreased in liver fibrosis, while the mechanism of miRNA-29b-3p in liver fibrosis has not been reported, and was elucidated in the work.

Methods

The miRNA-29b-3p levels were evaluated by q-PCR. The effect of miRNA-29b-3p on the activity of hepatic stellate cells was detected by cell activity assay. The protein levels were checked by western blot. The interaction between miRNA-29b-3p and ULK1 mRNA with base complementary sequences was detected by double luciferase assay. The autophagosomes were observed by TEM. The cell fibrosis-like change was evaluated with an anti-α-smooth muscle actin (α-SMA) antibody by IF.

Results

The results showed that miRNA-29b-3p mimics down-regulated the α-SMA and Col1 protein levels, and miRNA-29b-3p inhibitors upregulated the α-SMA and Col1 protein levels. The dual-luciferase assay result revealed that miRNA-29b-3p interacted with ULK1. The miRNA-29b-3p mimics inhibited the protein expression of ULK1, beclin1, and LC3, whereas miRNA-29b-3p inhibitors promoted the protein expression of ULK1, beclin1, and LC3.

Conclusion

The miRNA-29b-3p blocked HSCs trans-differentiation into myofibroblasts by inhibiting autophagy, and further inhibiting liver fibrosis in WD.

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2025-05-14
2025-09-14
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  • Article Type:
    Research Article
Keywords: ULK1 ; miRNA-29b-3p ; HSCs ; Wilson disease ; myofibroblasts ; Autophagy ; Liver fibrosis
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