Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung.
Pulmonary surfactant stabilizes lung alveoli, preventing respiratory failure and hyaline membrane disease in premature infants. In addition to lipids, surfactant contains apoproteins that are thought to be critical for normal surfactant function. We have examined the ontogeny and regulation of the major surfactant-associated protein of molecular mass 28-36 kDa (SP 28-36) in human fetal lung. SP 28-36 was not detected in tissue from second trimester abortuses by either immunoblot analysis or enzyme-linked immunosorbent assay (less than 0.02 microgram per mg of DNA). Levels of mRNA for SP 28-36, assayed by cDNA hybridization, were low or undetectable in all preculture specimens. The concentration of saturated phosphatidylcholine in lung tissue was 30% of the adult value with no apparent increase between 15 and 24 weeks gestation. SP 28-36 content increased during explant culture in the absence of serum and hormones, exceeding adult levels (3.2 +/- 1.0 micrograms per mg of DNA) after 5 days. In cultures treated with triiodothyronine (2 nM) and dexamethasone (10 nM), hormones that regulate phosphatidylcholine synthesis, the increase in SP 28-36 was accelerated (treated/control ratio was 7.1 and 3.4 at 3 and 5 days, respectively). Levels of mRNA for SP 28-36 also increased during culture and were stimulated by hormones (treated/control = 8.6 and 1.9 at 3 and 5 days, respectively). SP 28-36 and its mRNA increased similarly in the presence of dexamethasone alone, whereas triiodothyronine alone had no apparent effect. The molecular weight and charge pattern was similar for SP 28-36 of adult and cultured fetal tissue. These findings indicate that expression of the SP 28-36 gene is low during the second trimester, increases during explant culture, and is accelerated by glucocorticoid treatment.
Ballard
P L
PL
Hawgood
S
S
Liley
H
H
Wellenstein
G
G
Gonzales
L W
LW
Benson
B
B
Cordell
B
B
White
R T
RT
D001059:Apoproteins / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007526:Isoelectric Point; D008168:Lung / Q000196:embryology*; D008970:Molecular Weight; D010713:Phosphatidylcholines / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology
D001059:Apoproteins; D005938:Glucocorticoids; D010713:Phosphatidylcholines; D011510:Proteolipids; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014284:Triiodothyronine