STABILIZATION OF ELASTIN MESSENGER-RNA BY TGF-BETA - INITIAL CHARACTERIZATION OF SIGNALING PATHWAY

The cytokine transforming growth factor-beta (TGF-beta) has multiple e ffects on a wide variety of cell types. These effects include modulati on of growth and regulation of gene transcription In a few instances, TGF-beta has also been shown to regulate gene expression posttranscrip tionally 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 ela stin gene in cultured human fetal lung fibroblasts, but does stabilize elastin messenger RNA (mRNA), leading to a dramatic increase in the s teady-stare level of elastin mRNA. A corresponding increase in product ion of tropoelastin accompanies the increase in elastin mRNA. Through the use of specific inhibitors, we demonstrate that phosphatidylcholin e (PC)-specific phospholipase C (PLC) and protein kinase C (PKC) are i nvolved in mediating the elastin message stabilization. In contrast, G proteins and extracellularly regulated kinases do not appear to be in volved. These results suggest that although the TGF-beta signaling pat hway leading to message stabilization shares components with that modu lating transcription, the message-stabilization pathway also contains diverse other elements.