The effect of semaphorin 3E on angiogenesis in murine model of allergic asthma
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Date
2015
Authors
Tatari, Nazanin
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Abstract
Increased angiogenesis is an important characteristic of remodeling in asthmatic airways which stems from the imbalance between pro-angiogenic and anti-angiogenic factors. Surprisingly, the factors regulating this process in allergic asthma are poorly defined. The focus of this thesis is to investigate the effect of Semaphorin 3E (Sema3E) on angiogenesis events within the airways of murine model of allergic asthma.
The role of Sema3E in asthma angiogenesis was tested in wild type and Sema3e-/- mice exposed to House Dust Mite (HDM) and monitored for changes in blood vessels number in the lungs. In addition, the potential of Sema3E, in reversing features of allergen inflammation, was tested in mouse model. In both cases immunohistochemistry and immunofluorescence staining of lung tissues used to assess the changes in the level of angiogenesis. Moreover, the expression of pro- and anti-angiogenic factors in total lung homogenate was assessed by ELISA and Real-Time PCR.
The results showed that WT and Sema3e-/- mice both developed the HDM induced allergic asthma phenotype, but, the lung sections of HDM exposed Sema3e-/- mice had enhanced number of blood vessels compared to WT mice. The enhanced angiogenesis in Sema3-/- mice was coupled with increased level of angiogenesis driving factors VEGF and it receptor VEGFR-2. However, in WT mice the level of soluble VEGFR-1 secretion increased significantly which inhibited VEGF / VEGFR-2 binding.
Besides, Sema3E treatment reduced the level of angiogenesis and inhibited HDM-induced secretion of VEGF and the expression of its receptor VEGFR-2 while increased the level of soluble VEGFR-1. Analyzing the ratio of VEGF / soluble VEGFR-1 revealed that in the presence of Sema3E in both models, soluble VEGFR-1 is the dominant factor which has an inhibitory role on angiogenic effect of VEGF.
Taken together, this study provided the first evidence that Sema3E can modulate angiogenesis in allergic asthmatic airways.
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Keywords
Asthma, Angiogenesis, Semaphorin 3E