ApoL1 induces kidney inflammation through RIG-I/NF-κB activation

Area of Science:

• Nephrology
• Molecular Biology
• Genetics

Background:

• Genetic variations in the apolipoprotein L1 (APOL1) gene are linked to non-diabetic kidney diseases.
• The specific role of the ApoL1 protein in glomerular damage remains largely unclear.

Purpose of the Study:

• To investigate the function and underlying mechanisms of ApoL1 in causing glomerular damage.
• To identify key molecular pathways involved in ApoL1-mediated kidney injury.

Main Methods:

• Mice were treated with recombinant ApoL1 or phosphate buffer saline (PBS) for 3 months.
• Kidney tissue was analyzed using Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining, immunofluorescence, qRT-PCR, and ELISA.
• Microarray analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed.
• RIG-I knockdown in human podocytes and AAV-shRIG-I mice models were used to validate findings.

Main Results:

• ApoL1 treatment led to increased kidney inflammation, podocyte accumulation of ApoL1, and dose-dependent increases in inflammation and apoptotic markers.
• Microarray and pathway analyses identified the RIG-I/NF-κB signaling pathway as a key mediator of ApoL1-induced podocyte inflammation.
• Knockdown of RIG-I significantly reduced ApoL1-induced inflammatory and apoptotic markers in human podocytes and attenuated glomerular damage in mice.

Conclusions:

• ApoL1 contributes to glomerular damage by inducing abnormal expression of inflammatory molecules, primarily through the RIG-I/NF-κB signaling pathway.
• Targeting the RIG-I pathway may offer a novel therapeutic strategy for APOL1-associated kidney diseases.