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.
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 murinepulmonary 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 murinepulmonary 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.
Authors: Zachary T Rosenkrans; Christopher F Massey; Ksenija Bernau; Carolina A Ferreira; Justin J Jeffery; Jefree J Schulte; Melissa Moore; Frank Valla; Jeanine M Batterton; Christopher R Drake; Alan B McMillan; Nathan Sandbo; Ali Pirasteh; Reinier Hernandez Journal: Eur J Nucl Med Mol Imaging Date: 2022-05-12 Impact factor: 10.057