TY - JOUR
T1 - All trans-retinoic acid modulates hyperoxiainduced suppression of NF-kB-dependent Wnt signaling in alveolar A549 epithelial cells
AU - Tsotakos, Nikolaos
AU - Ahmed, Imtiaz
AU - Umstead, Todd M.
AU - Imamura, Yuka
AU - Yau, Eric
AU - Silveyra, Patricia
AU - Chroneos, Zissis C.
N1 - Publisher Copyright:
© 2022 Tsotakos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/8
Y1 - 2022/8
N2 - Introduction Despite recent advances in perinatal medicine, bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth. Inflammation, the main cause for BPD, results in arrested alveolarization. All trans-retinoic acid (ATRA), the active metabolite of Vitamin A, facilitates recovery from hyperoxia induced cell damage. The mechanisms involved in this response, and the genes activated, however, are poorly understood. In this study, we investigated the mechanisms of action of ATRA in human lung epithelial cells exposed to hyperoxia. We hypothesized that ATRA reduces hyperoxia-induced inflammatory responses in A549 alveolar epithelial cells. Methods A549 cells were exposed to hyperoxia with or without treatment with ATRA, followed by RNA-seq analysis. Results Transcriptomic analysis of A549 cells revealed ∼2,000 differentially expressed genes with a higher than 2-fold change. Treatment of cells with ATRA alleviated some of the hyperoxiainduced changes, including Wnt signaling, cell adhesion and cytochrome P450 genes, partially through NF-κB signaling. Discussion/Conclusion Our findings support the idea that ATRA supplementation may decrease hyperoxia-induced disruption of the neonatal respiratory epithelium and alleviate development of BPD.
AB - Introduction Despite recent advances in perinatal medicine, bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth. Inflammation, the main cause for BPD, results in arrested alveolarization. All trans-retinoic acid (ATRA), the active metabolite of Vitamin A, facilitates recovery from hyperoxia induced cell damage. The mechanisms involved in this response, and the genes activated, however, are poorly understood. In this study, we investigated the mechanisms of action of ATRA in human lung epithelial cells exposed to hyperoxia. We hypothesized that ATRA reduces hyperoxia-induced inflammatory responses in A549 alveolar epithelial cells. Methods A549 cells were exposed to hyperoxia with or without treatment with ATRA, followed by RNA-seq analysis. Results Transcriptomic analysis of A549 cells revealed ∼2,000 differentially expressed genes with a higher than 2-fold change. Treatment of cells with ATRA alleviated some of the hyperoxiainduced changes, including Wnt signaling, cell adhesion and cytochrome P450 genes, partially through NF-κB signaling. Discussion/Conclusion Our findings support the idea that ATRA supplementation may decrease hyperoxia-induced disruption of the neonatal respiratory epithelium and alleviate development of BPD.
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U2 - 10.1371/journal.pone.0272769
DO - 10.1371/journal.pone.0272769
M3 - Article
C2 - 35947545
AN - SCOPUS:85136339998
SN - 1932-6203
VL - 17
JO - PloS one
JF - PloS one
IS - 8 August
M1 - e0272769
ER -