Found in Inflammatory Zone 1 Induces Angiogenesis in Murine Models of Asthma

Abstract

Angiogenesis plays an important role in airway remodeling that occurs in asthma, while the mechanisms underlying this process are not fully elucidated. Found in inflammatory zone 1 (FIZZ1), a novel cysteine-rich secreted protein, is able to promote proliferation and migration of pulmonary endothelial cells, and to upregulate the expression of vascular endothelial growth factor (VEGF). However, the role of FIZZ1 in angiogenesis of asthma has not been fully investigated. Murine models of asthma were sensitized on days 1 and 14 by ovalbumin (OVA) and challenged with 2% OVA beginning from day 21. Mice were divided into four groups: asthmatic mice challenged with OVA for 7 days, 14 days, and 28 days, respectively, and healthy control mice that were sensititized and challenged with PBS. The expressions of FIZZ1, VEGF, and von Willebrand factor (vWF)-stained vascular area were measured in asthmatic mice and healthy controls (n = 10). Histologic examination was also performed on airway inflammation. Levels of FIZZ1 were increased significantly after allergic challenge, reached the peak by 7 days, declined by 14 days, and were reduced further by 28 days after OVA challenge. Similarly, percentages of vWF-stained vascular area (percentage of vascularity) were largely increased within 7 days and then reduced from day 14 of challenge. The expression of FIZZ1 in asthma was positively correlated with vWF-stained vascular area and VEGF expression in a time-dependent manner. FIZZ1 expression was significantly correlated with the percentage of vascularity and VEGF expression, suggesting that FIZZ1 and VEGF have crucial roles in angiogenesis of asthma.