Related Experiment Video
Updated: Mar 22, 2026
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
MicroRNA-421 induces hepatic mitochondrial dysfunction in non-alcoholic fatty liver disease mice by inhibiting
Yang Cheng1, Jingyin Mai2, Tianlu Hou1
1Institute of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Background And Aim:
Mitochondrial dysfunction plays a major role in critical initiating or propagating events in nonalcoholic fatty liver disease (NAFLD), but its pathogenesis remains obscure. Recently, microRNAs have been found to affect oxidant stress and lipid metabolism. In this study, we elucidated the functions of microRNA-421 in the development of NAFLD and identified its potential targets.
Methods:
An experimental model for the study of NAFLD was constructed by feeding a high fat diet to C57BL/6J mice. Differentially expressed miRNA in livers of NAFLD mice compared with controls were identified by high-throughput sequencing. Relative repression of luciferase expression standardized to a transfection control was analyzed by luciferase reporter assays.
Results:
The microRNA profiling presented that microRNA-421 expression was significantly upregulated in hepatic tissues of NAFLD model mouse. The sirtuin 3 was identified as a functionally relevant target of microRNA-421. The microRNA-421 acts upstream of SIRT3/FOXO3 pathway in modulation the oxidant stress and lipid metabolism. Overexpression of microRNA-421 decreased SIRT3 and FOXO3 protein levels, and then led to MnSOD and CAT decrease, the downstream targets of SIRT3/FOXO3 pathway. On the contrary, suppression of microRNA-421 had adverse effects on performance of celluar oxidative damage.
Conclusions:
Regulating or inhibiting hepatic microRNA-421 could decrease celluar oxidative damage and contribute to therapeutic potential in NAFLD.
Insights
Hepatic microRNA-421 is upregulated in nonalcoholic fatty liver disease (NAFLD), contributing to oxidative damage by targeting SIRT3. Inhibiting microRNA-421 may offer therapeutic potential for NAFLD.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Mitochondrial dysfunction is crucial in nonalcoholic fatty liver disease (NAFLD) pathogenesis.
- MicroRNAs regulate oxidant stress and lipid metabolism, but their role in NAFLD is unclear.
- This study investigates microRNA-421's function in NAFLD development.
Purpose of the Study:
- To elucidate the role of microRNA-421 in NAFLD.
- To identify microRNA-421 targets in the context of NAFLD.
- To explore microRNA-421's impact on oxidant stress and lipid metabolism in NAFLD.
Main Methods:
- Established a high-fat diet-induced NAFLD mouse model.
- Utilized high-throughput sequencing to identify differentially expressed microRNAs in NAFLD livers.
- Employed luciferase reporter assays to validate microRNA-421 targets.
Main Results:
- MicroRNA-421 expression was significantly upregulated in NAFLD mouse livers.
- Sirtuin 3 (SIRT3) was identified as a direct target of microRNA-421.
- MicroRNA-421 overexpression decreased SIRT3 and FOXO3, leading to reduced MnSOD and CAT, exacerbating oxidative damage.
Conclusions:
- MicroRNA-421 acts upstream of the SIRT3/FOXO3 pathway, modulating oxidant stress and lipid metabolism in NAFLD.
- Suppression of microRNA-421 improved cellular oxidative damage markers.
- Targeting hepatic microRNA-421 presents potential therapeutic strategies for NAFLD.
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs