Ontogeny of alpha 1- and beta 1-isoforms of Na(+)-K(+)-ATPase in fetal distal rat lung epithelium.
Because immature, in contrast to mature, fetal lungs have ineffective Na transport, we wished to determine the ontogeny of Na(+)-K(+)-ATPase expression in fetal distal lung epithelium (FDLE). FDLE and fibroblasts (FLF) from 17- to 22-day gestational age fetal rats (term = 22 days) were grown in primary culture. Northern and slot-blot analyses utilizing isoform-specific cDNA probes determined that alpha 1- (3.7 kb) and beta 1- (2.7, 2.3, and 1.9 kb) transcripts were present in FDLE at levels approximately fivefold higher than in FLF. alpha 2-, alpha 3-, or beta 2-isoforms of Na(+)-K(+)-ATPase were not detected. In 17-day gestational age FDLE, only small amounts of alpha 1-mRNA levels were detectable, and there were approximately 10-fold less beta 1-isoform transcripts. By 20 days gestational age, the level of alpha 1-transcripts roughly doubled, whereas beta 1-levels increased approximately sixfold. Thus, during the transition from the canalicular to saccular stages of lung development, FDLE have a differentially regulated surge in mRNA levels of alpha 1- and beta 1-Na(+)-K(+)-ATPase isoforms and do not switch isoforms during lung development. Levels for both isoform transcripts then fell before birth, reaching values less than those seen for 17-day gestational age FDLE. FDLE vesicle Na(+)-K(+)-ATPase activity did not increase until 22 days gestational age.
O'Brodovich
H
H
Respiratory Research Division, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Staub
O
O
Rossier
B C
BC
Geering
K
K
Kraehenbuhl
J P
JP
D000818:Animals; D000831:Animals, Newborn; D004591:Electrophoresis, Polyacrylamide Gel; D004848:Epithelium / Q000201:enzymology; D005333:Fetus; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008168:Lung / Q000196:embryology / Q000201:enzymology*; D011061:Poly A / Q000032:analysis / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
D007527:Isoenzymes; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D000254:Sodium-Potassium-Exchanging ATPase