AARS1 promotes diabetic kidney disease through rewiring Akt and NF-κB signaling to suppress autophagy and sustain inflammation - PubMed
2 hours ago
- #AARS1
- #Lactylation
- #Diabetic Kidney Disease
- AARS1 is upregulated in diabetic kidneys and lactylates Akt and NF-κB p65, enhancing their phosphorylation and activation.
- This lactylation leads to autophagy impairment, increased inflammatory cytokine expression, tubular injury, and macrophage accumulation.
- AARS1 controls transcription of genes like HK2, PFKP, ZEB1, and PPP6C, linking it to glycolytic reprogramming and fibrotic signaling.
- AARS1 operates in a glycolysis-lactate-NF-κB feedback loop, where lactate from glycolysis promotes NF-κB lactylation and activation, further increasing AARS1 transcription.
- Genetic knockout of Aars1 or treatment with β-alanine reduces lactylation, restores autophagy, decreases inflammation, and slows DKD progression in mouse models.
- The study identifies AARS1 as a metabolic-epigenetic amplifier and potential therapeutic target in diabetic kidney disease.