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Updated: Jul 14, 2025
Author Spotlight: Evaluating Therapeutic Strategies to Enhance Liver Regeneration
Published on: May 24, 2024
MicroRNA-181a-5p alleviates acute liver failure in mice by inhibiting HMGB1
Qianwen Zhang1, Yiyu He2, Hao Xu3
1Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266000, China. m15953373562@163.com.
Abstract:
MicroRNAs (miRNAs) control liver diseases, but the role of microRNA-181a-5p in acute liver failure (ALF) is unclear. In this study, the ALF model was generated by injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). The levels of miRNAs were assessed by microarray and qRT-PCR. The expression of caspase 3 was detected as the marker of cell apoptosis in ALF by immunohistochemistry and western blot. The targeting of microRNA-181a-5p on the high mobility group box 1 (HMGB1) was verified by dual luciferase assay. The impact of microRNA-181a-5p and HMGB1 was explored by flow cytometry. Results showed that microRNA-181a-5p was significantly down-regulated by D-GalN/LPS in vivo and in vitro, while the level of HMGB1 was up-regulated after the challenge. Furthermore, microRNA-181a-5p overexpression attenuated cell apoptosis in D-GalN/TNF-treated BNLCL2 cells. MicroRNA-181a-5p could directly target HMGB1 mRNA and repress its expressions, in further HMGB1 is involved in microRNA-181a-5p effect on cell apoptosis of ALF. In conclusion, these findings demonstrate that microRNA-181a-5p regulates hepatocyte apoptosis via HMGB1 in the development of ALF, which may provide potential therapeutic targets for ALF. However, the precise underlying mechanism that connects microRNA-181a-5p and HMGB1 remains to be explored.
Insights
MicroRNA-181a-5p is reduced in acute liver failure (ALF), leading to increased cell apoptosis via HMGB1. Restoring microRNA-181a-5p may offer a therapeutic strategy for ALF.
Area of Science:
- Molecular Biology
- Hepatology
- Biochemistry
Background:
- MicroRNAs (miRNAs) play a crucial role in regulating liver function and disease.
- The specific involvement of microRNA-181a-5p in the pathogenesis of acute liver failure (ALF) remains largely uncharacterized.
- Understanding miRNA-mediated mechanisms is vital for developing novel therapeutic interventions for liver diseases.
Purpose of the Study:
- To investigate the role of microRNA-181a-5p in the development of acute liver failure (ALF).
- To elucidate the molecular mechanism by which microRNA-181a-5p influences hepatocyte apoptosis in ALF.
- To identify potential therapeutic targets for ALF based on microRNA-181a-5p regulation.
Main Methods:
- An ALF model was established using D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in vivo and in vitro.
- MicroRNA expression profiling was performed using microarray and quantitative real-time PCR (qRT-PCR).
- Cell apoptosis was assessed by detecting caspase 3 expression (immunohistochemistry, Western blot) and flow cytometry; microRNA-181a-5p targeting of HMGB1 was confirmed by dual-luciferase assay.
Main Results:
- MicroRNA-181a-5p expression was significantly downregulated, while high mobility group box 1 (HMGB1) expression was upregulated in the ALF model.
- Overexpression of microRNA-181a-5p attenuated hepatocyte apoptosis in D-GalN/TNF-treated cells.
- MicroRNA-181a-5p directly targets HMGB1 mRNA, repressing its expression and influencing cell apoptosis in ALF.
Conclusions:
- MicroRNA-181a-5p plays a protective role in ALF by inhibiting hepatocyte apoptosis through the regulation of HMGB1.
- The microRNA-181a-5p/HMGB1 axis represents a potential therapeutic target for managing acute liver failure.
- Further research is warranted to fully delineate the intricate molecular mechanisms connecting microRNA-181a-5p and HMGB1 in ALF pathogenesis.
