Title | mRNA-induction of c-fos and the early growth response gene-1 in vascular smooth muscle cells by the platelet-derived growth factor isoforms | |
Authors | Ioannis Nouskas¹, Agapios Sachinidis² and Hans Vetter²
1. Medical Policlinic, Molecular Cardiology, University of Bonn, Germany (Head: Prof. Dr med. Hans Vetter) 2. Medical Policlinic, Cellular Biology Laboratories, University of Bonn, Germany (Head: Prof. Dr med. Hans Vetter) |
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Citation | Nouskas, I., Sachinidis, A., Vetter, H.: mRNA-induction of c-fos and the early growth response gene-1 in vascular smooth muscle cells by the platelet-derived growth factor isoforms, Epitheorese Klin. Farmakol. Farmakokinet. 7(3): 116-122 (1993) | |
Publication Date | Received for publication: 1 September 1993
Accepted for publication: 1 October 1993 |
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Full Text Language | English | |
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Keywords | PDGF-isoforms, Egr-1, c-fos, oligonucleotides. | |
Other Terms | review article | |
Summary | We focused this investigation on the effects of the platelet-derived growth factor (PDGF)-isoforms, PDGF-AA, PDGF-AB, and PDGF-BB on the mRNA-induction of the novel Early growth response gene-1 (Egr-1) and of the proto-oncogene c-fos in adult rat vascular smooth muscle cells (VSMCs). Induction of c-fos and Egr-1 mRNA has been associated with various significant cellular processes such as differentiation, development, hypertrophy and proliferation. In addition, applying the antisense approach we examined the role of Egr-1 in the PDGF-induced mitogenic effect in VSMCs. All three PDGF isoforms stimulated a similar time course of the c-fos and Egr-1 mRNA accumulations that reached maximal levels within 30 min. PDGF-AB and PDGF-BB induced a similar marked increase in cell DNA-synthesis. Although PDGF-AA induced c-fos and Egr-1 mRNA, it exerted only a poor mitogenic effect in this VSMC-model in comparison to PDGF-AB and PDGF-BB. An unmodified antisense oligodeoxyribonucleotide (20 bases) against the coding sequence of Egr-1 mRNA caused a significant 82% inhibition of the PDGF-BB-induced cell-DNA synthesis. Using modified (“mismatch”) antisense oligonucleotide sequences (20 bases) it could be shown that the inhibitory effect of the unmodified sequence is highly specific for the Egr-1 mRNA. These results provide direct evidence for the essential involvement of Egr-1 in the regulation of rat vascular smooth muscle cell growth. | |
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Online ISSN 1011-6575
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