Yes-associated protein induces age-dependent inflammatory signaling in the pulmonary endothelium.

Summary

In pneumonia-induced ALI, endothelial inflammatory signaling in adult (but not juvenile) mice required YAP, with transcriptomics showing enhanced NF-κB activation in adults. Pharmacologic or genetic blockade of YAP reduced inflammation, hypoxemia, and NF-κB nuclear translocation. These data implicate YAP as an age-dependent driver of endothelial inflammation relevant to ARDS pathobiology.

Key Findings

• Adult mice exhibited YAP-dependent endothelial inflammatory signaling in pneumonia-induced ALI; this was absent in 21-day-old weanlings.
• Endothelial transcriptomics showed increased NF-κB activation with ALI in adults versus juveniles.
• Blockade of YAP signaling protected against inflammatory response, hypoxemia, and NF-κB nuclear translocation.

Clinical Implications

While preclinical, targeting the YAP–NF-κB axis could attenuate endothelial-driven inflammation and hypoxemia in adult ALI/ARDS. Translation will require validation in human tissues and early-phase trials.

Limitations

• Preclinical animal study; human generalizability remains uncertain
• Cell-type specificity and long-term effects were not addressed in the abstract

Future Directions

Validate YAP–NF-κB axis in human ARDS endothelium, test pharmacologic inhibitors, and delineate endothelial cell–specific contributions across ages.