Developmental changes of tropoelastin synthesis by rat pulmonary fibroblasts and effects of dexamethasone.
Lung elastin is an important extracellular structural protein and it has been postulated that it plays a regulatory role in alveolar formation. To study the developmental regulation of elastin gene expression, we examined the tropoelastin (TE) production in primary culture of rat pulmonary fibroblasts (RPF). We found that developmental changes in elastin production as assessed by TE synthesis and 3.6-kb TE mRNA levels were similar for RPF and whole tissue except those results from late gestation animals, with peak elastin expression occurring 7 d postnatally with a decline out to 21 d. At late gestation (20 d), TE mRNA was barely detectable in RPF but clearly detectable TE mRNA in the whole tissue, indicating that there are elastogenic cells other than RPF in the tissue at this age. When TE-producing cells were treated with dexamethasone, there was a dose-dependent stimulation of TE synthesis with the maximum response at 10(-9) to 10(-7) M. Interestingly, dexamethasone had no stimulatory effect on cells from late gestation animals. The developmental window of elastin synthesis in this RPF model between late gestation and 21 d postnatal seems to correlate with the reported period of secondary alveolar formation, and thus we speculate that RPF elastogenic activity reflects that of the alveolar wall.
Noguchi
A
A
Pediatric Research Institute, Cardinal Glennon Children's Hospital, St. Louis University, School of Medicine, Missouri 63104.
Firsching
K
K
Kursar
J D
JD
Reddy
R
R
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005865:Gestational Age; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014333:Tropoelastin / Q000032:analysis / Q000096:biosynthesis*
D012333:RNA, Messenger; D014333:Tropoelastin; D003907:Dexamethasone