TY - JOUR
T1 - Altered epithelial cell proportions in the fetal lung of glucocorticoid receptor null mice
AU - Cole, Timothy James
AU - Solomon, Nicola M
AU - van Driel, Rosemary
AU - Monk, Julie A
AU - Bird, Daniel
AU - Richardson, Samantha J
AU - Dilley, Rodney James
AU - Hooper, Stuart Brian
PY - 2004/5
Y1 - 2004/5
N2 - Glucocorticoids provide important signals for maturation of the fetal lung and antenatal glucocorticoids are used to reduce the respiratory insufficiency suffered by preterm infants. To further understand the role of glucocorticoids in fetal lung maturation, we have analyzed mice with a targeted null mutation for the glucocorticoid receptor (CR) gene, which severely retards lung development. The lungs of fetal CR-null mice have increased lung weight and DNA content, are condensed and hypercellular, with reduced septal thinning leading to a 6-fold increase in the airway to capillary diffusion distance. In fetal CR-null mice, mRNA levels of the type II epithelial cell surfactant protein genes A and C were reduced by ∼ 50%. Analysis of epithelial cell types by electron microscopy revealed that the proportions of type II cells were increased by ∼ 30%, whereas the proportions of type-I cells were markedly reduced (by ∼ 50%). Similarly, we found a 50% reduction in mRNA levels for T1α and aquaporin-5, two type I cell-specific markers, and a 20% reduction in aquaporin-1 mRNA levels. This demonstrates that during murine embryonic development, receptor-mediated glucocorticoid signaling facilitates the differentiation of epithelial cells into type I cells, but is not obligatory for type II cell differentiation.
AB - Glucocorticoids provide important signals for maturation of the fetal lung and antenatal glucocorticoids are used to reduce the respiratory insufficiency suffered by preterm infants. To further understand the role of glucocorticoids in fetal lung maturation, we have analyzed mice with a targeted null mutation for the glucocorticoid receptor (CR) gene, which severely retards lung development. The lungs of fetal CR-null mice have increased lung weight and DNA content, are condensed and hypercellular, with reduced septal thinning leading to a 6-fold increase in the airway to capillary diffusion distance. In fetal CR-null mice, mRNA levels of the type II epithelial cell surfactant protein genes A and C were reduced by ∼ 50%. Analysis of epithelial cell types by electron microscopy revealed that the proportions of type II cells were increased by ∼ 30%, whereas the proportions of type-I cells were markedly reduced (by ∼ 50%). Similarly, we found a 50% reduction in mRNA levels for T1α and aquaporin-5, two type I cell-specific markers, and a 20% reduction in aquaporin-1 mRNA levels. This demonstrates that during murine embryonic development, receptor-mediated glucocorticoid signaling facilitates the differentiation of epithelial cells into type I cells, but is not obligatory for type II cell differentiation.
UR - http://www.scopus.com/inward/record.url?scp=2342474650&partnerID=8YFLogxK
U2 - 10.1165/rcmb.2003-0236OC
DO - 10.1165/rcmb.2003-0236OC
M3 - Article
C2 - 14578211
SN - 1044-1549
VL - 30
SP - 613
EP - 619
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
IS - 5
ER -