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Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma

Gene Therapy volume 11, pages 170–180 (2004)Cite this article

Abstract

Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. (In this study, working with a bleomycin(BLM)-induced scleroderma model mice, we performed two transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-β1 mRNA and the production of TGF-β1 on macrophage-like cells that infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.

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Acknowledgements

This work was partially supported by a grant (Nos. 08670952 and 10670781) from the Ministry of Education and a grant from Scleroderma Research Committee of Ministry of Health and Welfare. We thank Ms Motoko Sekiya for her excellent technical assistance.

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Authors and Affiliations

  1. Department of Dermatology and Immunodermatology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan

    M-H Wu, H Yokozeki, S Takagawa, T Yamamoto, T Satoh & K Nishioka

  2. Division of Gene Therapy Science, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan

    Y Kaneda

  3. Department of Dermatology, Nagasaki University, Nagasaki, Japan

    I Katayama

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  1. M-H Wu
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  2. H Yokozeki
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  3. S Takagawa
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  4. T Yamamoto
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  7. I Katayama
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Wu, MH., Yokozeki, H., Takagawa, S. et al. Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma. Gene Ther 11, 170–180 (2004). https://doi.org/10.1038/sj.gt.3302165

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