AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 491-L500, Copyright © 1995 by American Physiological Society
Glucocorticoids upregulate tropoelastin expression during late stages of fetal lung development
R. A. Pierce, W. I. Mariencheck, S. Sandefur, E. C. Crouch and W. C. Parks
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri.
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.
