[HTML][HTML] Calcineurin/Nfat signaling is required for perinatal lung maturation and function

V Davé, T Childs, Y Xu, M Ikegami… - The Journal of …, 2006 - Am Soc Clin Investig
V Davé, T Childs, Y Xu, M Ikegami, V Besnard, Y Maeda, SE Wert, JR Neilson, GR Crabtree
The Journal of clinical investigation, 2006Am Soc Clin Investig
Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung
immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a
common disorder contributing to morbidity and mortality in preterm infants. Surfactant
synthesis increases prior to birth in association with formation of the alveoli that mediate
efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the
Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse …
Pulmonary surfactant proteins and lipids are required for lung function after birth. Lung immaturity and resultant surfactant deficiency cause respiratory distress syndrome, a common disorder contributing to morbidity and mortality in preterm infants. Surfactant synthesis increases prior to birth in association with formation of the alveoli that mediate efficient gas exchange. To identify mechanisms controlling perinatal lung maturation, the Calcineurin b1 (Cnb1) gene was deleted in the respiratory epithelium of the fetal mouse. Deletion of Cnb1 caused respiratory failure after birth and inhibited the structural maturation of the peripheral lung. Synthesis of surfactant and a lamellar body–associated protein, ABC transporter A3 (ABCA3), was decreased prior to birth. Nuclear factor of activated T cells (Nfat) calcineurin-dependent 3 (Nfatc3), a transcription factor modulated by calcineurin, was identified as a direct activator of Sftpa, Sftpb, Sftpc, Abca3, Foxa1, and Foxa2 genes. The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing.
The Journal of Clinical Investigation