Marquez Hector A, Chen Felicia
Pulmonary Center, Boston University School of Medicine, 72 East Concord Street, Boston, MA, R-30402118, USA.
Subcell Biochem. 2020;95:151-174. doi: 10.1007/978-3-030-42282-0_6.
Retinoic acid (RA), the bioactive metabolite of vitamin A (VA), has long been recognized as a critical regulator of the development of the respiratory system. During embryogenesis, RA signaling is involved in the development of the trachea, airways, lung, and diaphragm. During postnatal life, RA continues to impact respiratory health. Disruption of RA activity during embryonic development produces dramatic phenotypes in animal models and human diseases, including tracheoesophageal fistula, tracheomalacia, congenital diaphragmatic hernia (CDH), and lung agenesis or hypoplasia. Several experimental methods have been used to target RA pathways during the formation of the embryonic lung. These have been performed in different animal models using gain- and loss-of-function strategies and dietary, pharmacologic, and genetic approaches that deplete retinoid stores or disrupt retinoid signaling. Experiments utilizing these methods have led to a deeper understanding of RA's role as an important signaling molecule that influences all stages of lung development. Current research is uncovering RA cross talk interactions with other embryonic signaling factors, such as fibroblast growth factors, WNT, and transforming growth factor-beta.
视黄酸（RA）是维生素A（VA）的生物活性代谢产物，长期以来一直被认为是呼吸系统发育的关键调节因子。在胚胎发生过程中，RA信号通路参与气管、气道、肺和膈肌的发育。在出生后，RA继续影响呼吸健康。胚胎发育过程中RA活性的破坏在动物模型和人类疾病中产生显著的表型，包括气管食管瘘、气管软化、先天性膈疝（CDH）以及肺不发育或发育不全。在胚胎肺形成过程中，已经使用了几种实验方法来靶向RA信号通路。这些实验在不同的动物模型中进行，采用功能获得和功能丧失策略以及饮食、药理学和遗传学方法，这些方法会耗尽类维生素A储备或破坏类维生素A信号。利用这些方法进行的实验使人们对RA作为影响肺发育各个阶段的重要信号分子的作用有了更深入的了解。目前的研究正在揭示RA与其他胚胎信号因子的相互作用，如成纤维细胞生长因子、WNT和转化生长因子-β。
