title: Luciferase expression is driven by the promoter of fibroblast activation protein-α in murine pulmonary fibrosis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institute of JingFeng Medical Laboratory Animal, 20 Dongdajie, Fengtai, Beijing, 100071, People's Republic of China, liwl@bmi.ac.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Wenlong
authors.forename: Yang
authors.initials: Y
authors.lastname: Leilei
authors.forename: Fan
authors.initials: F
authors.lastname: Wei
authors.forename: Chen
authors.initials: C
authors.lastname: Yi
authors.forename: Tian
authors.initials: T
authors.lastname: Jing
authors.forename: Ma
authors.initials: M
authors.lastname: Lanzhi
authors.forename: Liu
authors.initials: L
authors.lastname: Bing
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Wang
authors.initials: W
authors.lastname: Shaoxia
authors.forename: Fu
authors.initials: F
authors.lastname: Qiuxia
authors.forename: Chen
authors.initials: C
authors.lastname: Zeliang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zengming
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D010450:Endopeptidases; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D018093:Gelatinases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism*; D049408:Luminescent Agents / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D001761:Bleomycin; D010450:Endopeptidases; D018093:Gelatinases; D049409:Luciferases, Firefly; D049408:Luminescent Agents; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D053773:Transforming Growth Factor beta1; D000099167:Fibroblast Activation Protein Alpha; C508961:Tgfb1 protein, mouse