MicroRNA-146a-5p Negatively Regulates Inflammation via the Dectin-1/Syk/NF-κB Signaling Pathway in Aspergillus...

Area of Science:

• Ophthalmology
• Immunology
• Molecular Biology

Background:

• Fungal keratitis (FK) poses a significant threat to vision.
• The precise molecular mechanisms underlying FK pathogenesis require further elucidation.
• MicroRNAs (miRNAs) are emerging as key regulators of inflammatory diseases.

Purpose of the Study:

• To investigate the role of microRNA-146a-5p (miR-146a-5p) in the pathogenesis of fungal keratitis (FK).
• To explore the therapeutic potential of miR-146a-5p in mitigating FK-induced corneal damage.

Main Methods:

• Established a murine model of *Aspergillus fumigatus* ( *A. fumigatus* )-induced FK.
• Quantified miR-146a-5p expression levels during infection.
• Manipulated miR-146a-5p levels (overexpression and inhibition) to assess functional impact.
• Analyzed clinical severity, neutrophil infiltration, and pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α).
• Investigated the involvement of the Dectin-1/Syk/NF-κB signaling pathway.

Main Results:

• miR-146a-5p was significantly upregulated in the murine FK model.
• Overexpression of miR-146a-5p attenuated clinical severity and neutrophil infiltration.
• Inhibition of miR-146a-5p exacerbated corneal damage.
• miR-146a-5p downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
• miR-146a-5p suppressed the Dectin-1/Syk/NF-κB signaling pathway.

Conclusions:

• miR-146a-5p plays a crucial role in modulating inflammatory responses during fungal keratitis.
• miR-146a-5p exhibits protective effects against *A. fumigatus* infection-induced corneal damage.
• miR-146a-5p represents a potential therapeutic target for managing fungal keratitis.