دورية أكاديمية

Timing and cell specificity of senescence drives postnatal lung development and injury.

التفاصيل البيبلوغرافية
العنوان: Timing and cell specificity of senescence drives postnatal lung development and injury.
المؤلفون: Yao, Hongwei, Wallace, Joselynn, Peterson, Abigail L., Scaffa, Alejandro, Rizal, Salu, Hegarty, Katy, Maeda, Hajime, Chang, Jason L., Oulhen, Nathalie, Kreiling, Jill A., Huntington, Kelsey E., De Paepe, Monique E., Barbosa, Guilherme, Dennery, Phyllis A.
المصدر: Nature Communications; 1/17/2023, Vol. 14 Issue 1, p1-15, 15p
مصطلحات موضوعية: CELLULAR aging, LUNG development, LUNG injuries, MYOFIBROBLASTS
مستخلص: Senescence causes age-related diseases and stress-related injury. Paradoxically, it is also essential for organismal development. Whether senescence contributes to lung development or injury in early life remains unclear. Here, we show that lung senescence occurred at birth and decreased throughout the saccular stage in mice. Reducing senescent cells at this stage disrupted lung development. In mice (<12 h old) exposed to hyperoxia during the saccular stage followed by air recovery until adulthood, lung senescence increased particularly in type II cells and secondary crest myofibroblasts. This peaked during the alveolar stage and was mediated by the p53/p21 pathway. Decreasing senescent cells during the alveolar stage attenuated hyperoxia-induced alveolar and vascular simplification. Conclusively, early programmed senescence orchestrates postnatal lung development whereas later hyperoxia-induced senescence causes lung injury through different mechanisms. This defines the ontogeny of lung senescence and provides an optimal therapeutic window for mitigating neonatal hyperoxic lung injury by inhibiting senescence. Senescence causes age-related diseases and stress-related injury, but it is also physiologically essential during development. Here, Yao et al. show that programmed senescence in mesenchymal cells orchestrates postnatal lung development and that neonatal hyperoxia can induce senescence, particularly in type II, Pdgfra+ mesenchymal and immune cells, during the alveolar stage, resulting in lung injury. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:20411723
DOI:10.1038/s41467-023-35985-4