Retinoic acid increases surfactant protein mRNA in fetal rat lung in culture

1996 ◽  
Vol 271 (5) ◽  
pp. L862-L868 ◽  
Author(s):  
C. W. Bogue ◽  
H. C. Jacobs ◽  
D. W. Dynia ◽  
C. M. Wilson ◽  
I. Gross
Keyword(s):  
Retinoic Acid ◽  
Dose Response ◽  
Consensus Sequence ◽  
Surfactant Protein ◽  
Rat Lung ◽  
Response Element ◽  
Response Characteristics ◽  
Receptor Complexes ◽  
Fetal Rat ◽  
Fetal Rat Lung

Retinoic acid has both early or immediate (within hours) and late (after days) effects on gene expression. We studied the early effects of retinoic acid on the surfactant protein (SP) genes. Exposure of fetal rat lung explants to all trans-retinoic acid for 4 h resulted in a significant dose-dependent increase in SP-A, -B, and -C mRNA with markedly different dose-response characteristics. The maximal (2.5x) increase in SP-A mRNA was observed with 10(-10) M retinoic acid, whereas treatment with 10(-5) M resulted in a tendency to decreased levels. In contrast, maximal stimulation of SP-C (6x) was noted at 10(-5) M retinoic acid and that of SP-B (2x) at 10(-7) to 10(-5) M retinoic acid. Similar differences in the dose-response characteristics of SP-A and SP-C were observed with 9-cis-retinoic acid. A retinoic acid response element consensus sequence was identified in the rat SP-A gene; we hypothesize that retinoic acid-receptor complexes act directly on the SP-A gene via this response element.

Butyrate modulates surfactant protein mRNA in fetal rat lung by altering mRNA transcription and stability

1994 ◽  
Vol 267 (1) ◽  
pp. L9-L15 ◽  
Author(s):  
S. M. Peterec ◽  
K. V. Nichols ◽  
D. W. Dynia ◽  
C. M. Wilson ◽  
I. Gross
Keyword(s):  
Butyric Acid ◽  
Protein A ◽  
Maternal Diabetes ◽  
Surfactant Protein ◽  
Rat Lung ◽  
Mrna Transcription ◽  
Lung Maturation ◽  
Mrna Concentration ◽  
Fetal Rat ◽  
Fetal Rat Lung

We examined the effects of Na butyrate, a known regulator of gene expression, on surfactant protein mRNA concentration, transcription, and degradation. Exposure of explants of 18-day fetal rat lung to Na butyrate resulted in a decrease in surfactant protein A (SP-A) mRNA concentration to 7% of control after 6 h and to 18% of control after 24 h. The reduction in SP-A mRNA concentration was associated with decreased mRNA transcription and stability at both these times. The effects on SP-B mRNA were similar to those on SP-A, but quantitatively less. In contrast, butyrate had a biphasic effect on SP-C mRNA concentration. There was an initial decrease to 30% of control at 6 h, followed by an increase to control levels by 24 h. Transcription of SP-C was increased at both these times, whereas degradation was enhanced at 6 h, but not at 24 h. The level of surfactant protein mRNA after butyrate treatment therefore depends on the balance between induced changes in transcription and degradation. Butyrate had no effect on gamma-actin mRNA concentration in this system. Circulating levels of butyric acid analogues are elevated in the mothers and fetuses in diabetic pregnancies. Some of these fetuses have delayed lung maturation and decreased amniotic fluid SP-A levels. We speculate that butyric acid analogues partially mediate the changes in pulmonary maturation induced by maternal diabetes.

Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid

1995 ◽  
Vol 268 (4) ◽  
pp. L683-L690 ◽  
Author(s):  
Z. X. Xu ◽  
C. J. Viviano ◽  
S. A. Rooney
Keyword(s):  
Retinoic Acid ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fetal Lung ◽  
Late Gestation ◽  
Northern Analysis ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Stimulation Of

Glucocorticoid hormones are known to stimulate the rate of fatty acid biosynthesis and to increase the activity and mRNA level of fatty-acid synthase (FAS) in late gestation fetal lung. We have now examined the effect of dexamethasone on FAS transcription in fetal rat lung. Explants of 19-day fetal rat lung cultured for 48 h in serum-free medium were exposed to dexamethasone (10(-7) M) for various time periods. Nuclei were isolated, and the rate of [32P]UTP incorporation into FAS and gamma-actin RNA transcripts was measured by transcription-elongation assay. Dexamethasone increased FAS transcription but had no effect on that of actin. The maximum effect of the hormone, approximately threefold increase, was observed 1–2 h after addition of the hormone but was still apparent up to 48 h. FAS transcription but not that of actin was inhibited by cycloheximide and puromycin in both control and dexamethasone-treated cultures. However, the stimulatory effect of the hormone was not significantly reduced by the inhibitors. Retinoic acid antagonized the stimulatory effects of dexamethasone on FAS activity, mRNA content as measured by Northern analysis, mass as measured by Western blotting, and rate of transcription. The effect of retinoic acid was dependent on concentration in the relatively narrow range of 5 x 10(-6) to 5 x 10(-4) M. These data show that glucocorticoids stimulate transcription of the FAS gene in late gestation fetal rat lung, that normal transcription of the FAS gene is dependent on ongoing protein synthesis, and that glucocorticoid stimulation of FAS gene expression is antagonized by retinoic acid.

Regulation of surfactant protein A mRNA by hormones and butyrate in cultured fetal rat lung

1990 ◽  
Vol 259 (6) ◽  
pp. L488-L495 ◽  
Author(s):  
K. V. Nichols ◽  
J. Floros ◽  
D. W. Dynia ◽  
S. V. Veletza ◽  
C. M. Wilson ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Rat Lung ◽  
Acid Analogue ◽  
Camp Analogue ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Dose Dependent Fashion ◽  
Diabetic Mothers

We have previously shown that dexamethasone, triiodothyronine (T3) and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) stimulate phosphatidylcholine (PC) synthesis in fetal rat lung explants in culture. There are also additive interactions between these agents with regard to PC synthesis. In this study we examined the regulation of surfactant protein A (SP-A) mRNA in fetal rat lung in culture. Dexamethasone increased SP-A mRNA in the explants in a dose-dependent fashion (1–200 nM), but T3 did not. Whereas 8-bromo-cAMP increased SP-A mRNA, a decrease was observed with dibutyryl cAMP. These findings support the view that at least some of the genes involved in the synthesis of the various components of surfactant are independently regulated. Since we observed differences in the effects of a cAMP analogue which contained butyrate and one that did not, explants were then cultured with Na butyrate, a known regulator of gene expression. A significant decrease in SP-A mRNA was observed at mM concentrations. Exposure of the explants to alpha-aminobutyric acid, a butyric acid analogue which is elevated in the blood of infants of diabetic mothers, resulted in a significant decrease in SP-A mRNA at a concentration 1/25 of that required for Na butyrate. This observation raises the question of whether the decreased SP-A levels reported in fetuses of diabetic mothers may, at least in part, be related to this metabolite.

Hormonal Effects on the Surfactant Protein B (SP-B) mRNA in Cultured Fetal Rat Lung

1991 ◽  
Vol 4 (5) ◽  
pp. 449-454 ◽  
Author(s):  
Joanna Floros ◽  
Ian Gross ◽  
Katherine V. Nichols ◽  
Stavroula V. Veletza ◽  
Diane Dynia ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Rat Lung ◽  
Hormonal Effects ◽  
Surfactant Protein B ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Protein B
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