IGF-I regulation of elastogenesis: comparison of aortic and lung cells.
Rat neonatal aortic smooth muscle and pulmonary fibroblast cell cultures were exposed to different amounts of insulin-like growth factor-I (IGF-I, 1-100 ng/ml of medium) for 24 h. Aortic smooth muscle cells exhibited an increase in both steady-state levels of tropoelastin mRNA and soluble elastin with increasing amounts of IGF-I, suggesting that the growth factor is acting by increasing transcription or transcript stability. In contrast, pulmonary fibroblast cultures did not exhibit an elastogenic response to IGF-I because neither the steady-state levels of tropoelastin mRNA nor soluble elastin were affected. Transient transfection of the two cell cultures with a chimeric construct containing 500 bp of the elastin gene 5'-flanking region fused to the chloramphenicol acetyltransferase reporter gene showed that reporter activity was increased threefold in smooth muscle cells treated with IGF-I, whereas activity remains essentially the same in control and growth factor-treated pulmonary fibroblast cells. Receptor binding analyses revealed that both cell types possess the type I IGF-I receptor. Therefore, the lack of an elastogenic response in the lung cells cannot be attributed to lack of the appropriate receptor. These data, obtained in vitro with cell types that are principal producers of lung and aortic elastin, agree with results obtained in vivo. This agreement suggests that the regulation of elastin gene expression varies among cells derived from different tissues and furthermore provides model systems to investigate differential regulation of the elastin gene.
Rich
C B
CB
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Ewton
D Z
DZ
Martin
B M
BM
Florini
J R
JR
Bashir
M
M
Rosenbloom
J
J
Foster
J A
JA
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002478:Cells, Cultured; D002678:Chimera; D004547:Elastic Tissue / Q000254:growth & development*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005796:Genes; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D014333:Tropoelastin / Q000235:genetics
D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D014333:Tropoelastin; D007334:Insulin-Like Growth Factor I; D004549:Elastin