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Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis

Gene Therapy volume 24, pages 706–716 (2017)Cite this article

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a median survival of 3–4 years after diagnosis. It is the most frequent form of a group of interstitial pneumonias of unknown etiology. Current available therapies prevent deterioration of lung function but no therapy has shown to improve survival. Periostin is a matricellular protein of the fasciclin 1 family. There is increased deposition of periostin in lung fibrotic tissues. Here we evaluated whether small interfering RNA or antisense oligonucleotide against periostin inhibits lung fibrosis by direct administration into the lung by intranasal route. Pulmonary fibrosis was induced with bleomycin and RNA therapeutics was administered during both acute and chronic phases of the disease. The levels of periostin and transforming growth factor-β1 in airway fluid and lung tissue, the deposition of collagen in lung tissue and the lung fibrosis score were significantly reduced in mice treated with siRNA and antisense against periostin compared to control mice. These findings suggest that direct administration of siRNA or antisense oligonucleotides against periostin into the lungs is a promising alternative therapeutic approach for the management of pulmonary fibrosis.

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Acknowledgements

This research was supported in part by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Esteban C Gabazza), and research grants from Aqua Therapeutic Corporation. The funders had no role in study design, data analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. A Tomaru, T Kobayashi, J A Hinneh and C N D'Alessandro-Gabazza: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu, Japan

    A Tomaru, T Kobayashi, H Fujimoto, K Fujiwara, Y Takahashi & M Ohnishi

  2. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Japan

    J A Hinneh, P Baffour Tonto, C N D'Alessandro-Gabazza, T Yasuma, M Toda & E C Gabazza

  3. Department of Diabetes, Metabolism and Endocrinology, Mie University Graduate School of Medicine, Tsu, Japan

    T Yasuma & K Nishihama

  4. Department of Gastroenterology, Mie University Graduate School of Medicine, Tsu, Japan

    Y Takei

  5. Center for Mental and Physical Health, Mie University, Tsu, Japan

    O Taguchi

  6. Aqua Therapeutics Co., Ltd., Kobe, Japan

    M Yoshino, K Takao, T Totoki & K Yoshikawa

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  1. A Tomaru
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  2. T Kobayashi
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Corresponding author

Correspondence to E C Gabazza.

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Competing interests

MY, KT and KY are employees of Aqua Therapeutics Company and ECG received a Grant for Research from Aqua Therapeutics. The remaining authors declare no conflict of interest.

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Tomaru, A., Kobayashi, T., Hinneh, J. et al. Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis. Gene Ther 24, 706–716 (2017). https://doi.org/10.1038/gt.2017.80

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