Objectives: We used optical imaging of live animals and transgenic technology to develop a pulmonary fibrosis model in mice that can non-invasively and in real-time trace the pulmonary fibrosis process.
Results: Fibroblast activation protein-α (FAPα) is selectively expressed in fibrotic foci of human pulmonary fibrosis. It is not expressed in normal tissue. We confirmed that FAPα is upregulated in fibroblasts of murine pulmonary fibrosis. Moreover, TGF-β1, a central pathological mediator of fibrotic diseases, could promote FAPα expression in mouse embryonic fibroblasts. Luciferase reporter assays showed that 5.4 kb FAPα promoter response activities to TGF-β1 was stronger than of the 2.1 kb promoter. We generated a transgenic mouse line expressing firefly luciferase under the control of the 5.4 kb FAPα gene promoter (FAPα-p-luc). After experimentally inducing murine pulmonary fibrosis, there luminescence appeared in the chests and excised lungs of FAPα-p-luc mice. The intensity of luminescence became stronger with the exacerbation of pulmonary fibrosis.
Conclusion: Fluorescence intensity reflects the degree of pulmonary fibrosis in FAPα-p-luc mice. and this mouse model may be used to investigate molecular mechanisms and drug screening of pulmonary fibrosis.