Stabilization of elastin mRNA by TGF-β: initial characterization of signaling pathway
U Kucich, JC Rosenbloom, WR Abrams… - American journal of …, 1997 - atsjournals.org
U Kucich, JC Rosenbloom, WR Abrams, MM Bashir, J Rosenbloom
American journal of respiratory cell and molecular biology, 1997•atsjournals.orgThe cytokine transforming growth factor-β (TGF-β) 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-β 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-β1 has no
effect on transcription of the elastin gene in cultured human fetal lung fibroblasts, but does …
cell types. These effects include modulation of growth and regulation of gene transcription.
In a few instances, TGF-β 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-β1 has no
effect on transcription of the elastin gene in cultured human fetal lung fibroblasts, but does …
The cytokine transforming growth factor-β (TGF-β) 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-β 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-β1 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-β signaling pathway leading to message stabilization shares components with that modulating transcription, the message-stabilization pathway also contains diverse other elements.
ATS Journals