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Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice

Pulmonary fibrosis is a known sequela of severe or persistent lung damage. Existing clinical, imaging and autopsy studies have shown that the lungs exhibit a pathological pulmonary fibrosis phenotype after infection with coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-...

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Autores principales: Li, Xiaohe, Liu, Rui, Cui, Yunyao, Liang, Jingjing, Bi, Zhun, Li, Shimeng, Miao, Yang, Zhang, Liang, Li, Xiaoping, Zhou, Honggang, Yang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427522/
https://www.ncbi.nlm.nih.gov/pubmed/34512328
http://dx.doi.org/10.3389/fphar.2021.692346
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author Li, Xiaohe
Liu, Rui
Cui, Yunyao
Liang, Jingjing
Bi, Zhun
Li, Shimeng
Miao, Yang
Zhang, Liang
Li, Xiaoping
Zhou, Honggang
Yang, Cheng
author_facet Li, Xiaohe
Liu, Rui
Cui, Yunyao
Liang, Jingjing
Bi, Zhun
Li, Shimeng
Miao, Yang
Zhang, Liang
Li, Xiaoping
Zhou, Honggang
Yang, Cheng
author_sort Li, Xiaohe
collection PubMed
description Pulmonary fibrosis is a known sequela of severe or persistent lung damage. Existing clinical, imaging and autopsy studies have shown that the lungs exhibit a pathological pulmonary fibrosis phenotype after infection with coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary fibrosis may be one of the most serious sequelae associated with coronavirus disease 2019 (COVID-19). In this study, we aimed to examine the preventative effects of the antiviral drug remdesivir on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of remdesivir on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of remdesivir in lung fibroblasts and alveolar epithelial cells in vitro. The preventive remdesivir treatment was started on the day of bleomycin installation, and the results showed that remdesivir significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro experiments showed that remdesivir dose-dependently suppressed TGF-β1-induced lung fibroblast activation and improved TGF-β1-induced alveolar epithelial to mesenchymal transition. Our results indicate that remdesivir can preventatively alleviate the severity of pulmonary fibrosis and provide some reference for the prevention of pulmonary fibrosis in patients with COVID-19.
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spelling pubmed-84275222021-09-10 Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice Li, Xiaohe Liu, Rui Cui, Yunyao Liang, Jingjing Bi, Zhun Li, Shimeng Miao, Yang Zhang, Liang Li, Xiaoping Zhou, Honggang Yang, Cheng Front Pharmacol Pharmacology Pulmonary fibrosis is a known sequela of severe or persistent lung damage. Existing clinical, imaging and autopsy studies have shown that the lungs exhibit a pathological pulmonary fibrosis phenotype after infection with coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pulmonary fibrosis may be one of the most serious sequelae associated with coronavirus disease 2019 (COVID-19). In this study, we aimed to examine the preventative effects of the antiviral drug remdesivir on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of remdesivir on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of remdesivir in lung fibroblasts and alveolar epithelial cells in vitro. The preventive remdesivir treatment was started on the day of bleomycin installation, and the results showed that remdesivir significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro experiments showed that remdesivir dose-dependently suppressed TGF-β1-induced lung fibroblast activation and improved TGF-β1-induced alveolar epithelial to mesenchymal transition. Our results indicate that remdesivir can preventatively alleviate the severity of pulmonary fibrosis and provide some reference for the prevention of pulmonary fibrosis in patients with COVID-19. Frontiers Media S.A. 2021-08-26 /pmc/articles/PMC8427522/ /pubmed/34512328 http://dx.doi.org/10.3389/fphar.2021.692346 Text en Copyright © 2021 Li, Liu, Cui, Liang, Bi, Li, Miao, Zhang, Li, Zhou and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Xiaohe
Liu, Rui
Cui, Yunyao
Liang, Jingjing
Bi, Zhun
Li, Shimeng
Miao, Yang
Zhang, Liang
Li, Xiaoping
Zhou, Honggang
Yang, Cheng
Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title_full Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title_fullStr Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title_full_unstemmed Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title_short Protective Effect of Remdesivir Against Pulmonary Fibrosis in Mice
title_sort protective effect of remdesivir against pulmonary fibrosis in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427522/
https://www.ncbi.nlm.nih.gov/pubmed/34512328
http://dx.doi.org/10.3389/fphar.2021.692346
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