Retinoic acid increases surfactant protein mRNA in fetal rat lung in culture.
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.
Bogue
C W
CW
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Jacobs
H C
HC
Dynia
D W
DW
Wilson
C M
CM
Gross
I
I
D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D005091:Exons; D005333:Fetus; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D011510:Proteolipids / Q000096:biosynthesis* / Q000302:isolation & purification; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014212:Tretinoin