Authors
QiuXiang Xu, XiaoLi Tian, Bin Li, Jian Kang
Published in
Advanced biology. Volume 10. Issue 7. Pages e00321.
Abstract
Bronchopulmonary dysplasia (BPD), a debilitating chronic respiratory condition afflicting preterm neonates, stems from oxidative injury and is characterized by arrested alveolar growth and aberrant inflammatory responses. This investigation uncovers a novel mechanistic axis in which the 20-hydroxyeicosatetraenoic acid (20-HETE)/GPR75 signaling cascade acts as a previously unrecognized driver of NLRP1 inflammasome activation in neonatal BPD, thereby linking oxidative stress to inflammatory signaling via p53. Using murine hyperoxia models, we observe that excessive oxygen exposure selectively upregulates GPR75 expression and 20-HETE biosynthesis within alveolar epithelial cells. Genetic inactivation of Gpr75 in vivo significantly attenuated hyperoxia-induced lung injury, oxidative stress, and NLRP1-dependent secretion of interleukin-1β and interleukin-18. Mechanistic dissection revealed that 20-HETE induces NLRP1 inflammasome assembly in rat alveolar epithelia via p53-mediated signaling. In vitro corroboration via lentiviral-mediated Gpr75 silencing, with scrambled shRNA serving as a negative control, further validated its role in hyperoxia-triggered NLRP1 activation and cytokine release (P < 0.01 vs. scrambled control). Collectively, these findings establish the 20-HETE/GPR75 axis as a critical regulator of inflammasome-dependent pathogenesis in BPD. Blockade of this axis inhibits inflammasome assembly and downstream inflammation by suppressing p53 signaling. These results highlight this axis as a promising therapeutic target to mitigate oxygen-induced injury and inflammatory sequelae in preterm infants.
PMID:
42489007
Bibliographic data and abstract were imported from PubMed on 23 Jul 2026.
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