MiR-548a-3p regulates inflammatory response via TLR4/NF-κB signaling pathway in rheumatoid arthritis

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) and exosome-encapsulated miRNAs are implicated in rheumatoid arthritis (RA) pathogenesis.
• Exosomes-encapsulated miR-548a-3p was previously found to be decreased in RA patient serum.
• The specific role of miR-548a-3p in RA development and progression remains largely unknown.

Purpose of the Study:

• To investigate the molecular mechanisms of miR-548a-3p in rheumatoid arthritis (RA).
• To provide insights into RA pathogenesis.
• To identify novel therapeutic targets for RA.

Main Methods:

• Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate miRNA expression.
• Expression levels of miR-548a-3p were analyzed in serum exosomes and peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls.
• Associations between serum exosomal miR-548a-3p levels and RA disease markers (CRP, RF, ESR) were examined.
• The effect of miR-548a-3p on pTHP-1 cell proliferation and activation was assessed, focusing on the TLR4/NF-κB signaling pathway.

Main Results:

• miR-548a-3p expression was significantly down-regulated in serum exosomes and PBMCs of RA patients compared to healthy controls.
• Serum exosomal miR-548a-3p levels showed a negative correlation with C-reactive protein (CRP), rheumatoid factor (RF), and erythrocyte sedimentation rate (ESR) in RA patients.
• miR-548a-3p demonstrated an inhibitory effect on pTHP-1 cell proliferation and activation by regulating the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway.

Conclusions:

• Exosomes-delivered miR-548a-3p may serve as a crucial biomarker for predicting RA disease activity.
• The miR-548a-3p/TLR4/NF-κB axis represents a promising target for the diagnosis and treatment of rheumatoid arthritis.