Oligonucleotide-targeting periostin ameliorates pulmonary fibrosis
Autor: | Yoshiyuki Takei, Esteban C. Gabazza, Hajime Fujimoto, Corina N. D’Alessandro-Gabazza, Josephine A. Hinneh, Kazumasa Takao, M. Ohnishi, Taro Yasuma, Masaaki Toda, Kota Nishihama, K Yoshikawa, P Baffour Tonto, Osamu Taguchi, Tetsu Kobayashi, Yoshinori Takahashi, Toshiaki Totoki, Kentaro Fujiwara, M Yoshino, Atsushi Tomaru |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Small interfering RNA Pulmonary Fibrosis Oligonucleotides Biology Periostin Bleomycin Mice 03 medical and health sciences Idiopathic pulmonary fibrosis chemistry.chemical_compound 0302 clinical medicine Transforming Growth Factor beta Fibrosis Pulmonary fibrosis Genetics medicine Animals RNA Small Interfering Lung Molecular Biology Administration Intranasal Matricellular protein Fibroblasts Oligonucleotides Antisense respiratory system medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Cancer research Molecular Medicine Female Collagen Cell Adhesion Molecules |
Zdroj: | Gene Therapy. 24:706-716 |
ISSN: | 1476-5462 0969-7128 |
Popis: | 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. |
Databáze: | OpenAIRE |
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