H3K18 lactylation-mediated SPHK1-SIRT1 feedback loop accelerates pyroptosis of tubular epithelial cells in sepsis-associated acute kidney injury - PubMed
4 days ago
- #lactylation
- #SA-AKI
- #pyroptosis
- Lactate accumulation worsens sepsis-associated acute kidney injury (SA-AKI) by promoting renal tubular epithelial cell (RTEC) pyroptosis.
- SPHK1 was identified as a key mediator in lactate-augmented pyroptosis, with its inhibition alleviating the condition.
- Nicotinamide adenine dinucleotide (NAD+) was found to suppress SPHK1 expression and RTEC injury marker KIM-1, showing therapeutic potential.
- A feedback loop involving H3K18 lactylation, SPHK1, and SIRT1 was discovered, driving NLRP3 inflammasome-mediated pyroptosis in SA-AKI.
- Combining NAD+ supplementation with SPHK1 inhibition presents a novel therapeutic strategy for SA-AKI.