Glucocorticoids upregulate tropoelastin expression during late stages of fetal lung development.
The production of elastin, an essential extracellular matrix protein of terminal airway interstitium, occurs mostly during early development. Because glucocorticoids influence airway maturation, we studied the effect of dexamethasone (Dex) on tropoelastin expression during fetal lung development. Timed-pregnant rats were treated with Dex (1 mg/kg daily), and fetal lungs were collected 3 days later at 17, 19, and 21 days of gestation. Dex treatment resulted in about a threefold increase in tropoelastin mRNA levels at 19 days concomitant with accelerated airway development. By in situ hybridization, Dex treatment increased the number of tropoelastin-expressing cells and the level of tropoelastin mRNA per cell. In organ culture, Dex increased lung tropoelastin expression and augmented cortisol stimulation of tropoelastin expression. In fetal pulmonary artery smooth muscle cells, 10(-8) M Dex upregulated tropoelastin mRNA expression and increased tropoelastin promoter-chloramphenicol acetyl transferase activity in transient transfections. These data indicate that pharmacologically administered glucocorticoids transcriptionally upregulate fetal lung tropoelastin expression and suggest that steroid hormones may be important regulators of elastin production in vivo.
Pierce
R A
RA
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri.
Mariencheck
W I
WI
Sandefur
S
S
Crouch
E C
EC
Parks
W C
WC
D000818:Animals; D015152:Blotting, Northern; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006854:Hydrocortisone / Q000494:pharmacology; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology* / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D014333:Tropoelastin / Q000235:genetics*
D012333:RNA, Messenger; D014333:Tropoelastin; D003907:Dexamethasone; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D015500:Chloramphenicol O-Acetyltransferase; D006854:Hydrocortisone