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Published on: October 23, 2018
MicroRNA-125a-5p Contributes to Hepatic Stellate Cell Activation through Targeting FIH1
Background/Aims:
Emerging evidence shows that microRNAs (miRNAs) play a crucial role in the regulation of activation, proliferation and apoptosis of hepatic stellate cells (HSCs). Previous studies have indicated that miR-125a-5p is correlated with hepatitis B virus replication and disease progression. However, little is known about the biological role and underlying mechanism of miR-125a-5p in liver fibrosis.
Methods:
We analyzed the level of miR-125a-5p in carbon tetrachloride-induced liver fibrosis and activated HSCs. We analyzed the effects of miR-125a-5p down-regulation on HSC activation and proliferation. We also analyzed the binding of miR-125a-5p to the 3'-untranslated region of factor inhibiting hypoxia-inducible factor 1 (FIH1) mRNA.
Results:
Up-regulation of miR-125a-5p was observed in the liver tissues of fibrotic mice and activated HSCs. Down-regulation of miR-125a-5p prevented the activation and proliferation of HSCs. FIH1, a negative modulator of hypoxia inducible factor 1, was confirmed to be a target of miR-125a-5p using the luciferase reporter assay. Further studies demonstrated that miR-125a-5p prompted the activation and proliferation of HSCs, at least in part, by down-regulating FIH1.
Conclusion:
Our findings shed new light on miRNAs as a promising therapeutic target in liver fibrosis.
Insights
MicroRNA-125a-5p promotes liver fibrosis by activating hepatic stellate cells (HSCs) through down-regulating FIH1. Targeting this microRNA (miRNA) pathway offers a potential therapeutic strategy for liver fibrosis.
Area of Science:
- Molecular biology
- Hepatology
- Biochemistry
Background:
- MicroRNAs (miRNAs) regulate hepatic stellate cell (HSC) activation, proliferation, and apoptosis.
- miR-125a-5p is linked to hepatitis B virus replication and disease progression.
- The specific role of miR-125a-5p in liver fibrosis remains largely unknown.
Purpose of the Study:
- To investigate the biological role of miR-125a-5p in liver fibrosis.
- To elucidate the underlying mechanism of miR-125a-5p in HSC activation and proliferation.
- To identify potential therapeutic targets for liver fibrosis.
Main Methods:
- Analysis of miR-125a-5p levels in carbon tetrachloride-induced liver fibrosis and activated HSCs.
- Assessment of miR-125a-5p down-regulation effects on HSC activation and proliferation.
- Luciferase reporter assay to confirm the binding of miR-125a-5p to the 3'-untranslated region of factor inhibiting hypoxia-inducible factor 1 (FIH1) mRNA.
Main Results:
- miR-125a-5p was up-regulated in fibrotic liver tissues and activated HSCs.
- Down-regulation of miR-125a-5p inhibited HSC activation and proliferation.
- FIH1 was identified as a direct target of miR-125a-5p, and miR-125a-5p promoted HSC activation and proliferation by down-regulating FIH1.
Conclusions:
- miR-125a-5p plays a significant role in promoting liver fibrosis by regulating HSCs.
- The miR-125a-5p/FIH1 axis is a key mechanism in liver fibrosis progression.
- miRNAs, particularly miR-125a-5p, represent promising therapeutic targets for liver fibrosis.
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