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Regulation of pulmonary surfactant apoprotein SP 28-36 gene in fetal human lung
Insights
The expression of surfactant protein SP 28-36 in human fetal lungs is low in the second trimester but increases with development. Glucocorticoids significantly accelerate this expression, crucial for lung maturation.
Area of Science:
- Pulmonary medicine
- Developmental biology
- Biochemistry
Background:
- Pulmonary surfactant is vital for alveolar stability and preventing respiratory distress in premature infants.
- Surfactant apoproteins, including SP 28-36, are critical for surfactant function.
- The developmental expression of SP 28-36 in human fetal lungs requires further investigation.
Purpose of the Study:
- To investigate the ontogeny and regulation of the major surfactant-associated protein, SP 28-36, in human fetal lung development.
- To determine the influence of hormones on SP 28-36 gene expression and protein synthesis.
Main Methods:
- Immunoblot analysis and ELISA were used to quantify SP 28-36 protein levels.
- cDNA hybridization assessed messenger RNA (mRNA) levels for SP 28-36.
- Human fetal lung explants were cultured with and without hormones (triiodothyronine and dexamethasone).
Main Results:
- SP 28-36 protein and mRNA were undetectable or low in second-trimester fetal lung tissue.
- SP 28-36 levels significantly increased during explant culture, exceeding adult levels.
- Hormonal treatment, particularly with dexamethasone, accelerated SP 28-36 expression and mRNA levels.
Conclusions:
- SP 28-36 gene expression is significantly upregulated during late fetal lung development.
- Glucocorticoids play a key role in accelerating SP 28-36 expression.
- These findings highlight the hormonal regulation of surfactant protein synthesis during lung maturation.
Abstract:
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.