Involvement of {gamma}-secretase in postnatal angiogenesis
- Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)
- Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka 565-0871 (Japan)
{gamma}-Secretase cleaves the transmembrane domains of several integral membrane proteins involved in vasculogenesis. Here, we investigated the role of {gamma}-secretase in the regulation of postnatal angiogenesis using {gamma}-secretase inhibitors (GSI). In endothelial cell (EC), {gamma}-secretase activity was up-regulated under hypoxia or the treatment of vascular endothelial growth factor (VEGF). The treatment of GSI significantly attenuated growth factor-induced EC proliferation and migration as well as c-fos promoter activity in a dose-dependent manner. In vascular smooth muscle cell (VSMC), treatment of GSI significantly attenuated growth factor-induced VEGF and fibroblast growth factor-2 (FGF-2) expression. Indeed, GSI attenuated VEGF-induced tube formation and inhibited FGF-2-induced angiogenesis on matrigel in mice as quantified by FITC-lectin staining of EC. Overall, we demonstrated that {gamma}-secretase may be key molecule in postnatal angiogenesis which may be downstream molecule of growth factor-induced growth and migration in EC, and regulate the expression of angiogenic growth factors in VSMC.
- OSTI ID:
- 21032981
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 363; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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