All trans-retinoic acid modulates hyperoxia-induced suppression of NF-kB-dependent Wnt signaling in alveolar A549 epithelial cells.

Autor: Nikolaos Tsotakos, Imtiaz Ahmed, Todd M Umstead, Yuka Imamura, Eric Yau, Patricia Silveyra, Zissis C Chroneos
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS ONE, Vol 17, Iss 8, p e0272769 (2022)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0272769
Popis: IntroductionDespite 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.MethodsA549 cells were exposed to hyperoxia with or without treatment with ATRA, followed by RNA-seq analysis.ResultsTranscriptomic 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 hyperoxia-induced changes, including Wnt signaling, cell adhesion and cytochrome P450 genes, partially through NF-κB signaling.Discussion/conclusionOur findings support the idea that ATRA supplementation may decrease hyperoxia-induced disruption of the neonatal respiratory epithelium and alleviate development of BPD.
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje