Involvement of {gamma}-secretase in postnatal angiogenesis

Journal Article · Fri Nov 23 00:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.09.003· OSTI ID:21032981

Hayashi, Hiroki ^[1]; Nakagami, Hironori ^[1]; Takami, Yoichi ^[1]; Sato, Naoyuki ^[2]; Saito, Yukihiro; Nishikawa, Tomoyuki; Mori, Masaki; Koriyama, Hiroshi; Tamai, Katsuto ^[1]; Morishita, Ryuichi ^[2]; Kaneda, Yasufumi ^[1]

---

1. Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)
2. 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, Vol. 363, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.09.003; PII: S0006-291X(07)01957-2; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANOXIA
CELL PROLIFERATION
FIBROBLASTS
GROWTH FACTORS
MEMBRANE PROTEINS
MICE
MOLECULES
MUSCLES
PROMOTERS