Moderate hyperoxia induces senescence in developing human lung fibroblasts.

Moderate hyperoxia induces senescence in developing human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 14;: Authors: You K, Parikh P, Khandalavala K, Wicher S, Manlove LJ, Yang B, Roesler AM, Roos B, Teske JJ, Britt RD, Pabelick CM, Prakash YS Abstract Hyperoxia exposure in premature infants increases the risk of subsequent lung diseases such as asthma and bronchopulmonary dysplasia. Fibroblasts help maintain bronchial and alveolar integrity. Thus understanding mechanisms by which hyperoxia influences fibroblasts is critical. Cellular senescence is increasingly recognized as important to pathophysiology of multiple diseases. We hypothesized that clinically-relevant moderate hyperoxia (<50% O2) induces senescence in developing fibroblasts. Using primary human fetal lung fibroblasts, we investigated effects of 40% O2 on senescence, ER stress and autophagy pathways. Fibroblasts were exposed to 21% or 40% O2 for 7 days with etoposide as positive control to induce senescence, evaluated by morphological changes, β-galactosidase activity, and DNA damage markers. Senescence-associated secretory phenotype (SASP) profile of inflammatory and pro-fibrotic markers was further assessed. Hyperoxia decreased proliferation but increased cell size. SA-β-gal activity and DNA damage response, cell cycle arrest in G2/M phase and marked upregulation of phosphorylated p53 and p21 were noted. Reduced autophagy was noted with hyperoxia...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research