Peptide ToAP3 from T. obscurus interferes with idiopathic pulmonary fibrosis progression in murine model

Karina Smidt Simon,Cesar Melo-Silva, Paulo Henrique Veloso, Luisa Coelho,João Paulo Longo,Leonora Vianna, Verônica Amado,Anamélia Bocca

EUROPEAN RESPIRATORY JOURNAL(2019)

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摘要
This work explores the use of immunomodulatory peptide ToAP3 from T. obscurus in a murine model of idiopathic pulmonary fibrosis (IPF) aiming to evaluate this its potential as a new pharmacological therapy. IPF is a rare, deadly, specific form of chronic progressive fibrosing interstitial pneumonia of unknown cause occurring in adults, limited to the lungs. Treatments for this nosological entity are limited and only able to delay the disease’s progression. They were developed to interfere directely with fibrotic process with no pupose of interfering with local immune response, which has been considered key to the maintenance IPF’s progression. Therefore, we used bleomycin intratracheally instilated mice treated each 3 days with ToAP3, starting at the beginning of fibrotic process, to evaluate its ability of interfere with IPF’s progression as a immunomodulatory agent. We verified that ToAP3 is a effective treatment for the disease by analyzing the pulmonary tissue, ventilatory mechanics and gene modulation in lung tissue. ToAP3 was able estabilize the lung tissue on the same conditions of the beginning of the treatment. Accordingly, we found that the respiratory state of treated animals was highly increased. Also, we could notice that at the end of treatment many pro-fibrotic genes such as Itgb6, Tgfb1, Tgfb2, Tgfb3, Tgfbr1 and Tgfb2 were down regulated. These results indicate that ToAP3 were able to interfere effectively in IPF progression on the evaluated time, thus representing a new potential therapy for this disease.
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关键词
Idiopathic pulmonary fibrosis,Anti-inflammatory,Animal models
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