Fra-2 overexpressing mice were initially described as a model of systemic sclerosis associated organ fibrosis, with predominant alterations in the lung.
In this study we analyzed how blocking TGFβ signaling affects pulmonary abnormalities in Fos-related antigen 2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important lung pathological features of SSc: fibrosis, inflammation, and vascular remodeling.
Consistent with these observations, a strong MMP10 staining of the thickened wall of distal pulmonary arteries was found both in the lungs of patients with SSc-associated PH and in the lungs of Fra-2-Tg mice.
Under this situation, three new genetic animal models have recently been established, such as Fra2 transgenic mice, urokinase-type plasminogen activator receptor deficient mice and Klf5(+/-) ;Fli1(+/-) mice, all of which recapitulate the pathological cascade of SSc.
The Fra-2 (Fos-related antigen-2) transgenic mouse model simultaneously displays both pro-fibrotic and vascular characteristics of human systemic sclerosis.
Stimulation with TGFbeta and platelet-derived growth factor (PDGF) significantly increased the expression of Fra-2 in SSc fibroblasts and induced DNA binding of Fra-2 in an ERK-dependent manner.