MicroRNA-409-3p regulates macrophage migration in polymyositis through targeting CXCR4
1Department of Pulmonary Medicine, Ningbo HwaMei Hospital, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, P. R. China.
Background:
Macrophage migration and infiltration contribute to the pathogenesis of polymyositis (PM). This study aims to investigate the effect and underlying mechanism of miR-409-3p on macrophage migration in PM.
Methods:
The GSE143845 database was used to predict the altered expression of microRNAs (miRNAs) in PM. The quantitative real-time PCR (qRT-PCR), western blot and Transwell assay were performed to detect migration of macrophages and expressions of related molecules. A luciferase activity assay was conducted to confirm the binding of miR-409-3p and CXCR4 3'-UTR. Next, a mouse model of experimental autoimmune myositis (EAM) was established. Haematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to measure associated factors.
Results:
MiR-409-3p was downregulated in PM of GSE143845 database and patients. Differently, the serum creatine kinase (s-CK), TNF-α, and IL-6 in patients with PM were increased. Furthermore, miR-409-3p mimic transfection reduced the migration of macrophages and CXCR4 levels, while miR-409-3p inhibitor exerted the opposite effects. CXCR4 was a target of miR-409-3p, and the effect of CXCR4 on promoting macrophage migration was reversed by miR-409-3p mimic. In vivo, miR-409-3p agomir injection reduced inflammatory cells, macrophages, and TNFα and IL-6 levels in muscles and serum of EAM mouse models.
Conclusions:
In conclusion, miR-409-3p reduces the migration of macrophages through negatively regulating CXCR4 expression in PM.
Insights
MicroRNA-409-3p (miR-409-3p) is reduced in polymyositis (PM) and inhibits macrophage migration by targeting CXCR4. Restoring miR-409-3p levels may offer a therapeutic strategy for PM.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Macrophage migration is crucial in polymyositis (PM) pathogenesis.
- Understanding the regulatory mechanisms of macrophage migration in PM is vital.
Purpose of the Study:
- To investigate the role and mechanism of microRNA-409-3p (miR-409-3p) in regulating macrophage migration in PM.
Main Methods:
- Bioinformatic analysis (GSE143845 database) and qRT-PCR to assess miRNA expression.
- Transwell assays, Western blot, and luciferase assays to evaluate macrophage migration and molecular interactions.
- Establishment of an experimental autoimmune myositis (EAM) mouse model for in vivo validation.
Main Results:
- miR-409-3p was significantly downregulated in PM patients and database samples.
- miR-409-3p mimic reduced macrophage migration and CXCR4 expression, while inhibitor increased them.
- CXCR4 was identified as a direct target of miR-409-3p, and its pro-migratory effect was reversed by miR-409-3p.
- In vivo studies showed miR-409-3p agomir reduced inflammation and macrophage infiltration in EAM mice.
Conclusions:
- miR-409-3p acts as a negative regulator of macrophage migration in PM by targeting CXCR4.
- Restoring miR-409-3p levels presents a potential therapeutic avenue for polymyositis.
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