Peng Huang, Yuzhe Huang, Ting Dong, Yulong Yang, Wei He, Meixia Wang, Han Wang, Wenming Yang
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miRNA-29b-3p: An Important Target for Ameliorating Liver Fibrosis in Wilson Disease by Inhibiting Autophagy.
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.
期刊介绍：
Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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