TY - JOUR
T1 - Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with dexamethasone
AU - Ingbar, David H.
AU - Duvick, Sara
AU - Savick, S. Kay
AU - Schellhase, Dennis E.
AU - Detterding, Robin
AU - Jamieson, James D.
AU - Shannon, John M.
PY - 1997/4
Y1 - 1997/4
N2 - Late in gestation, the prenatal fetal alveolar epithelium switches from fluid secretion to resorption of salt and water via apical sodium channels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because maternal glucocorticoids (GC) may promote maturation of the alveolar epithelium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase α- and β-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it at FD19. Northern analysis of total lung RNA for the (α1- and β1-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, β1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas α1-mRNA was not altered. There were accompanying increases in β1-, but not α1-, protein. At FD19, GC treatment for 5 days (FD14-FD18 increased β1- and decreased α1-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the α1-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, maternal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased β1-mRNA levels dependent on duration of treatment and fetal age.
AB - Late in gestation, the prenatal fetal alveolar epithelium switches from fluid secretion to resorption of salt and water via apical sodium channels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because maternal glucocorticoids (GC) may promote maturation of the alveolar epithelium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase α- and β-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it at FD19. Northern analysis of total lung RNA for the (α1- and β1-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, β1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas α1-mRNA was not altered. There were accompanying increases in β1-, but not α1-, protein. At FD19, GC treatment for 5 days (FD14-FD18 increased β1- and decreased α1-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the α1-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, maternal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased β1-mRNA levels dependent on duration of treatment and fetal age.
KW - alveolar fluid
KW - glucocorticoids
KW - sodium pump
KW - sodium-potassium- adenosinetriphosphatase
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U2 - 10.1152/ajplung.1997.272.4.l665
DO - 10.1152/ajplung.1997.272.4.l665
M3 - Article
C2 - 9142940
AN - SCOPUS:0030909776
SN - 1040-0605
VL - 272
SP - L665-L672
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 4 16-4
ER -