miR-3146 induces neutrophil extracellular traps to aggravate gout flare
Lizhen Shan1, Di Yang2, Fabo Feng2
1Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Gout is an inflammatory arthritis and is characterized by the accumulation of deposited monosodium urate (MSU) crystals in the joints. miRNAs may act as key regulators of gout pathogenesis. The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of gout.
Methods:
The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time reverse transcription-polymerase chain reaction and Western blot, respectively. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. Gout model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs.
Results:
Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with gout, which was accompanied with the higher levels of NETs. MSU crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with gout.
Conclusion:
Our findings indicated that miR-3146-mediated NETs formation may play a potential role in the pathogenesis of gout. These results suggested that miR-3146 could be used as a potential therapeutic target for the treatment of gout.
Insights
MicroRNA-3146 (miR-3146) is elevated in gout patients and promotes neutrophil extracellular trap (NETs) formation. Inhibiting miR-3146 effectively reduced NETs in a rat gout model, suggesting it as a potential therapeutic target.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Gout is an inflammatory arthritis caused by monosodium urate (MSU) crystal deposition.
- MicroRNAs (miRNAs) are implicated as key regulators in gout pathogenesis.
- Neutrophil extracellular traps (NETs) are increasingly recognized in inflammatory joint diseases.
Purpose of the Study:
- To investigate the role of miR-3146 in neutrophil extracellular trap (NET) formation during gout pathogenesis.
- To elucidate the molecular mechanism underlying miR-3146's function in gout.
Main Methods:
- Quantified miR-3146 and SIRT1 expression using RT-PCR and Western blot.
- Assessed targeting relationship between miR-3146 and SIRT1 via luciferase reporter assay.
- Measured reactive oxygen species (ROS) and NETs formation using fluorescent staining, immunofluorescence, and ELISA.
- Utilized a rat gout model to evaluate therapeutic effects of miR-3146 inhibition.
Main Results:
- miR-3146 expression and NETs were significantly increased in neutrophils of gout patients.
- MSU crystals stimulated miR-3146 expression, ROS production, and NETs formation.
- miR-3146 directly targets and regulates SIRT1.
- Antagomir-3146 therapy effectively suppressed NETs formation in a rat gout model.
Conclusions:
- miR-3146 promotes gout pathogenesis through the induction of NETs formation.
- miR-3146 represents a promising therapeutic target for gout treatment.
