LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p

Area of Science:

• Neuroscience
• Molecular Biology
• Immunology

Background:

• Neuroinflammation is a key factor in traumatic brain injury (TBI) pathology.
• Long non-coding RNA maternally expressed gene 3 (Meg3) influences microglial activation and inflammation.
• The precise molecular targets and pathways of Meg3 in TBI require further investigation.

Purpose of the Study:

• To elucidate the role of Meg3 in TBI-induced neuroinflammation.
• To identify the molecular targets and signaling pathways regulated by Meg3.
• To investigate the therapeutic potential of targeting the Meg3 pathway in TBI.

Main Methods:

• Lipopolysaccharide (LPS) + ATP stimulation in microglia models.
• Quantitative real-time PCR and Western blotting.
• MicroRNA (miRNA) analysis, bioinformatic predictions, and dual-luciferase reporter assays.
• Overexpression and knockdown experiments for Meg3 and miR-7a-5p.

Main Results:

• LPS + ATP upregulated Meg3, enhanced microglial activation, Nlrp3/caspase1 pathway activation, and inflammation, while decreasing miR-7a-5p.
• Meg3 directly targets and negatively regulates miR-7a-5p.
• Meg3 functions as a competing endogenous RNA (ceRNA) for miR-7a-5p.
• Meg3 promotes microglial inflammation by regulating nod-like receptor protein 3 (Nlrp3) expression via the miR-7a-5p/Nlrp3 pathway.

Conclusions:

• Meg3 exacerbates TBI-induced neuroinflammation by modulating the miR-7a-5p/Nlrp3 pathway.
• Meg3 acts as a crucial regulator of microglial activation and inflammatory responses in TBI.
• The Meg3/miR-7a-5p/Nlrp3 axis represents a potential therapeutic target for TBI treatment.