RUNX2 and USP16 stabilize MFRN2 to maintain pulmonary epithelial barrier integrity in sepsis-induced acute lung injury - PubMed
6 hours ago
- #ferroptosis
- #RUNX2
- #sepsis-induced ALI
- RUNX2 is identified as a key mediator in sepsis-induced acute lung injury, specifically affecting pulmonary epithelial cells without involving macrophage activation.
- Lipopolysaccharide (LPS) stimulation increases RUNX2 binding to the USP16 promoter, leading to transcriptional activation of USP16.
- Activated USP16 removes K27-linked ubiquitin chains from mitoferrin-2 (MFRN2) at lysine 97, causing mitochondrial iron imbalance and promoting epithelial ferroptosis.
- The aryl hydrocarbon receptor (AHR) interacts with RUNX2 to inhibit its activation, thereby reducing epithelial apoptosis.
- Targeting RUNX2 transcriptional activation could potentially enhance epithelial resistance to injury in sepsis.