title: Heterologous Matrix Metalloproteinase Gene Promoter Activity AllowsIn VivoReal-time Imaging of Bleomycin-Induced Lung Fibrosis in Transiently Transgenized Mice.
abstract: Idiopathic pulmonary fibrosis is a very common interstitial lung disease derived from chronic inflammatory insults, characterized by massive scar tissue deposition that causes the progressive loss of lung function and subsequent death for respiratory failure. Bleomycin is used as the standard agent to induce experimental pulmonary fibrosis in animal models for the study of its pathogenesis. However, to visualize the establishment of lung fibrosis after treatment, the animal sacrifice is necessary. Thus, the aim of this study was to avoid this limitation by using an innovative approach based on a double bleomycin treatment protocol, along with thein vivoimages analysis of bleomycin-treated mice. A reporter gene construct, containing the luciferase open reading frame under the matrix metalloproteinase-1 promoter control region, was tested on double bleomycin-treated mice to investigate, in real time, the correlation between bleomycin treatment, inflammation, tissue remodeling and fibrosis. Bioluminescence emitted by the lungs of bleomycin-treated mice, corroborated by fluorescent molecular tomography, successfully allowed real time monitoring of fibrosis establishment. The reporter gene technology experienced in this work could represent an advanced functional approach for real time non-invasive assessment of disease evolution during therapy, in a reliable and translational living animal model.
authors.affiliation: Chiesi Farmaceutici S.p.A., Corporate Pre-Clinical R&D , Parma , Italy.
authors.forename: Fabio Franco
authors.initials: FF
authors.lastname: Stellari
authors.affiliation: Chiesi Farmaceutici S.p.A., Corporate Pre-Clinical R&D , Parma , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ruscitti
authors.affiliation: Chiesi Farmaceutici S.p.A., Corporate Pre-Clinical R&D, Parma, Italy; Dipartimento di Scienze Medico Veterinarie, Università di Parma, Parma, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pompilio
authors.affiliation: Dipartimento di Scienze Medico Veterinarie, Università di Parma , Parma , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ravanetti
authors.affiliation: Dipartimento di Scienze Medico Veterinarie, Università di Parma , Parma , Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tebaldi
authors.affiliation: Dipartimento di Scienze Medico Veterinarie, Università di Parma , Parma , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Macchi
authors.affiliation: Dipartimento di Scienze Medico Veterinarie, Università di Parma , Parma , Italy.
authors.forename: Andrea Elizabeth
authors.initials: AE
authors.lastname: Verna
authors.affiliation: Chiesi Farmaceutici S.p.A., Corporate Pre-Clinical R&D , Parma , Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Villetti
authors.affiliation: Dipartimento di Scienze Medico Veterinarie, Università di Parma , Parma , Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Donofrio
keywords: bioluminescence; bleomycin; fluorescent molecular tomography; idiopathic pulmonary fibrosis; matrix metalloproteinase-1 promoter