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Luciferase expression is driven by the promoter of fibroblast activation protein-α in murine pulmonary fibrosis

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Abstract

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.

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Abbreviations

BLI:

Bioluminescence imaging

BLM:

Bleomycin

ECM:

Extracellular matrix

EGR1:

Early growth response 1

FAPα:

Fibroblast activation protein-α

IPF:

Idiopathic pulmonary fibrosis

Luc:

Luciferase

MEFs:

Mouse embryonic fibroblasts

IPF:

Idiopathic pulmonary fibrosis

TGF-β1:

Transforming growth factor-β1

Tg:

Transgenic

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Acknowledgments

We thank Dr. Tao Zhou, Ms Weili Gong for performing in vivo BLI, Dr. Xing Huang for careful review of the manuscript. We would like to thank staff of the Institute of JingFeng Medical Laboratory Animal for animal husbandry. This work was supported by the National Natural Science Foundation of China (31101679).

Conflict of interest

The authors state no conflict of interest.

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    Authors and Affiliations

    1. Institute of JingFeng Medical Laboratory Animal, 20 Dongdajie, Fengtai, Beijing, 100071, People’s Republic of China

      Li Wenlong, Fan Wei, Ma Lanzhi & Liu Bing

    2. Beijing Institute of Radiation Medicine, Beijing, 100850, People’s Republic of China

      Yang Leilei, Li Yang & Wang Shaoxia

    3. Institute of Biotechnology, Beijing, 100071, People’s Republic of China

      Chen Yi

    4. Institute of Military Medical, Chengdu Military Region’s Center for Disease Control and Prevention, Kunming, 650032, People’s Republic of China

      Tian Jing

    5. Beijing Institute of Transfusion Medicine, Beijing, 100850, People’s Republic of China

      Fu Qiuxia

    6. Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China

      Chen Zeliang & Zhao Zengming

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    1. Li Wenlong
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    2. Yang Leilei
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    3. Fan Wei
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    Correspondence to Li Wenlong.

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    Li Wenlong and Yang Leilei have contributed equally to this work.

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    Wenlong, L., Leilei, Y., Wei, F. et al. Luciferase expression is driven by the promoter of fibroblast activation protein-α in murine pulmonary fibrosis. Biotechnol Lett 37, 1757–1763 (2015). https://doi.org/10.1007/s10529-015-1855-8

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    • DOI: https://doi.org/10.1007/s10529-015-1855-8

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