Stabilization of elastin mRNA by TGF-beta: initial characterization of signaling pathway.
The cytokine transforming growth factor-beta (TGF-beta) has multiple effects on a wide variety of cell types. These effects include modulation of growth and regulation of gene transcription. In a few instances, TGF-beta has also been shown to regulate gene expression posttranscriptionally by altering message stability, but the pathway by which this activity is executed remains largely unknown. In the present work, we demonstrate that TGF-beta 1 has no effect on transcription of the elastin gene in cultured human fetal lung fibroblasts, but does stabilize elastin messenger RNA (mRNA), leading to a dramatic increase in the steady-state level of elastin mRNA. A corresponding increase in production of tropoelastin accompanies the increase in elastin mRNA. Through the use of specific inhibitors, we demonstrate that phosphatidylcholine (PC)-specific phospholipase C (PLC) and protein kinase C (PKC) are involved in mediating the elastin message stabilization. In contrast, G proteins and extracellularly regulated kinases do not appear to be involved. These results suggest that although the TGF-beta signaling pathway leading to message stabilization shares components with that modulating transcription, the message-stabilization pathway also contains diverse other elements.
Kucich
U
U
Department of Anatomy and Histology, University of Pennsylvania School of Dental Medicine, Philadelphia 19104, USA.
Rosenbloom
J C
JC
Abrams
W R
WR
Bashir
M M
MM
Rosenbloom
J
J
D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004549:Elastin / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005333:Fetus; D005347:Fibroblasts; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009636:Norbornanes; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D009636:Norbornanes; D012333:RNA, Messenger; D013859:Thiocarbamates; D013871:Thiones; D016212:Transforming Growth Factor beta; C061465:calphostin complex; C046498:tricyclodecane-9-yl-xanthogenate; D004549:Elastin; D010738:Type C Phospholipases; D019311:Staurosporine