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Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence
Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharma...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768023/ https://www.ncbi.nlm.nih.gov/pubmed/33381023 http://dx.doi.org/10.3389/fphar.2020.553690 |
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author | Zhang, Li Tong, Xiang Huang, Jizhen Wu, Man Zhang, Shijie Wang, Dongguang Liu, SiTong Fan, Hong |
author_facet | Zhang, Li Tong, Xiang Huang, Jizhen Wu, Man Zhang, Shijie Wang, Dongguang Liu, SiTong Fan, Hong |
author_sort | Zhang, Li |
collection | PubMed |
description | Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-β/Smad3 in vivo. In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-7768023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77680232020-12-29 Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence Zhang, Li Tong, Xiang Huang, Jizhen Wu, Man Zhang, Shijie Wang, Dongguang Liu, SiTong Fan, Hong Front Pharmacol Pharmacology Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-β/Smad3 in vivo. In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-β/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis. Frontiers Media S.A. 2020-12-14 /pmc/articles/PMC7768023/ /pubmed/33381023 http://dx.doi.org/10.3389/fphar.2020.553690 Text en Copyright © 2020 Zhang, Tong, Huang, Wu, Zhang, Dongguang, Liu and Fan http://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 Zhang, Li Tong, Xiang Huang, Jizhen Wu, Man Zhang, Shijie Wang, Dongguang Liu, SiTong Fan, Hong Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title | Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title_full | Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title_fullStr | Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title_full_unstemmed | Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title_short | Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence |
title_sort | fisetin alleviated bleomycin-induced pulmonary fibrosis partly by rescuing alveolar epithelial cells from senescence |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768023/ https://www.ncbi.nlm.nih.gov/pubmed/33381023 http://dx.doi.org/10.3389/fphar.2020.553690 |
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