ARP2 Promotes Angiogenesis but Not Permeability in Vascular Vessels

Abstract

Abstract: : Purpose: Angiopoietin signaling through Tie2 receptor has been shown to regulate angiogenesis, which is essential for pathophysiological condition. Recently, we cloned four structurally homologous proteins containing characteristic coiled–coil domain at the N–terminus and a fibrinogen–like domain at the C–terminus. In this study, we analyzed the biological function of ARP2 in vascular vessels. Methods: We analyzed whether ARP2 promoted proliferative and chemotactic activity in vitro, and angiogenesis in vivo using corneal assay. We generated transgenic mice expressing ARP2 in epidermal keratinocytes (K14–ARP2 Tg) and analyzed histological examination of vessels and permeability of ear in K14–ARP2 Tg mice. Results: ARP2 directly promoted chemotactic activity, but not affect the proliferation of vascular endothelial cells in vitro, and promoted angiogenesis in vivo. K14–ARP2 Tg mice exhibited reddish ears and snout. Histological examination of ear in K14–ARP2 Tg mice revealed that capillary vessels in ear skin were enlarged. Vascular permeability analysis demonstrated that K14–ARP2 Tg mice did not promote vascular leakage. Conclusions: These vascular phenotypes were similar to those of K14–Ang1 transgenic mice. Based on these findings, it is possible that biological functions of ARP2 could lead to novel therapeutic strategies for leaky vessels, such as diabetic macular edema.

Keywords: gene/expression