An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

International Immunopharmacology
Tetsuya NishimotoCarol A Feghali-Bostwick

Abstract

Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) was orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20 μg of oral E4 peptide ameliorated the fibrosis. The low...Continue Reading

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Citations

Feb 13, 2016·Frontiers in Pharmacology·Sylvie Ricard-Blum, Sylvain D Vallet
Dec 23, 2017·Journal of Scleroderma and Related Disorders·Sara M GarrettCarol Feghali-Bostwick
Dec 5, 2017·Biological & Pharmaceutical Bulletin·Muneyoshi OkadaHideyuki Yamawaki
Jun 26, 2018·International Journal of Molecular Sciences·Katsuyuki TanabeJun Wada
Mar 13, 2018·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Muneyoshi Okada, Hideyuki Yamawaki
Oct 8, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Xinh-Xinh NguyenCarol Feghali-Bostwick
Nov 15, 2017·Matrix Biology : Journal of the International Society for Matrix Biology·Sylvie Ricard-Blum, Sylvain D Vallet

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