Cortistatin antagonizes Piezo1-STING axis and facilitates mitochondrial homeostasis of keratinocytes by attenuating AGEs accumulation in diabetic ulcers - PubMed
5 hours ago
- #Cortistatin
- #Piezo1
- #Diabetic ulcers
- Mechanical stress induces glucose accumulation and metabolic stress in keratinocytes.
- Piezo1 activation leads to glucose overload and AGEs accumulation, causing mtDNA leakage and activating the cGAS-STING pathway.
- Keratinocyte-specific Piezo1 deletion reduces AGEs accumulation and preserves mitochondrial integrity.
- STING ablation shows protective effects similar to Piezo1 deletion.
- Cortistatin (CST) is identified as an inhibitory ligand of Piezo1, attenuating calcium influx and glucose accumulation under mechanical stress.
- CST-Piezo1-STING axis integrates mechanical and metabolic cues driving keratinocyte dysfunction in diabetes.
- CST provides notable protection in vitro and in diabetic ulcer models.