CLEC7A Knockdown Alleviates Ischemic Stroke by Inhibiting Pyroptosis and Microglia Activation

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Ischemic stroke (IS) is a leading global cause of mortality.
• Identifying novel biomarkers is crucial for understanding and treating IS.
• The role of C-type lectin domain family 7 member A (CLEC7A) in IS requires further investigation.

Purpose of the Study:

• To identify novel biomarkers for ischemic stroke (IS).
• To explore the specific role of C-type lectin domain family 7 member A (CLEC7A) in IS pathogenesis.
• To investigate the therapeutic potential of targeting CLEC7A in IS.

Main Methods:

• Screened differentially expressed genes (DEGs) from public IS datasets (GSE106680, GSE97537, GSE61616).
• Constructed protein-protein interaction networks to identify hub genes, including CLEC7A.
• Utilized middle cerebral artery occlusion and reperfusion (MCAO/R) in a rat model; assessed neural function, cell viability (OGD/R), inflammation (ELISA), and gene/protein expression (RT-qPCR, Western Blotting).

Main Results:

• CLEC7A was identified as a significant hub gene associated with IS.
• MCAO/R induced microglial activation and pyroptosis, increasing inflammatory markers (IL-1β, IL-18, TNF-α).
• CLEC7A knockdown reduced infarct volume, improved neurological scores, enhanced cell viability, and inhibited pyroptosis and microglial activation in IS models.

Conclusions:

• CLEC7A serves as a promising biomarker for ischemic stroke.
• Targeting CLEC7A by knockdown demonstrates a therapeutic effect in IS.
• Inhibition of pyroptosis and microglial activation by CLEC7A knockdown is the underlying mechanism for alleviating IS.