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Potential role of senescent macrophages in radiation-induced pulmonary fibrosis
Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141056/ https://www.ncbi.nlm.nih.gov/pubmed/34023858 http://dx.doi.org/10.1038/s41419-021-03811-8 |
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author | Su, Lulu Dong, Yinping Wang, Yueying Wang, Yuquan Guan, Bowen Lu, Yanhua Wu, Jing Wang, Xiaochun Li, Deguan Meng, Aimin Fan, Feiyue |
author_facet | Su, Lulu Dong, Yinping Wang, Yueying Wang, Yuquan Guan, Bowen Lu, Yanhua Wu, Jing Wang, Xiaochun Li, Deguan Meng, Aimin Fan, Feiyue |
author_sort | Su, Lulu |
collection | PubMed |
description | Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there’s a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal(+) senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF. |
format | Online Article Text |
id | pubmed-8141056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81410562021-06-07 Potential role of senescent macrophages in radiation-induced pulmonary fibrosis Su, Lulu Dong, Yinping Wang, Yueying Wang, Yuquan Guan, Bowen Lu, Yanhua Wu, Jing Wang, Xiaochun Li, Deguan Meng, Aimin Fan, Feiyue Cell Death Dis Article Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation in clinic with poor prognosis and limited therapeutic options. Previous results have shown that senescent cells, such as fibroblast and type II airway epithelial cell, are strongly implicated in pathology of RIPF. However, the role of senescent macrophages in the development RIPF is still unknown. In this study, we report that ionizing radiation (IR) increase cellular senescence with higher expression of senescence-associated β-galactosidase (SA-β-Gal) and senescence-specific genes (p16, p21, Bcl-2, and Bcl-xl) in irradiated bone marrow-derived monocytes/macrophages (BMMs). Besides, there’s a significant increase in the expression of pro-fibrogenic factors (TGF-β1 and Arg-1), senescence-associated secretory phenotype (SASP) proinflammatory factors (Il-1α, Il-6, and Tnf-α), SASP chemokines (Ccl2, Cxcl10, and Ccl17), and SASP matrix metalloproteinases (Mmp2, Mmp9 and Mmp12) in BMMs exposed to 10 Gy IR. In addition, the percentages of SA-β-Gal(+) senescent macrophages are significantly increased in the macrophages of murine irradiated lung tissue. Moreover, robustly elevated expression of p16, SASP chemokines (Ccl2, Cxcl10, and Ccl17) and SASP matrix metalloproteinases (Mmp2, Mmp9, and Mmp12) is observed in the macrophages of irradiated lung, which might stimulate a fibrotic phenotype in pulmonary fibroblasts. In summary, irradiation can induce macrophage senescence, and increase the secretion of SASP in senescent macrophages. Our findings provide important evidence that senescent macrophages might be the target for prevention and treatment of RIPF. Nature Publishing Group UK 2021-05-22 /pmc/articles/PMC8141056/ /pubmed/34023858 http://dx.doi.org/10.1038/s41419-021-03811-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Su, Lulu Dong, Yinping Wang, Yueying Wang, Yuquan Guan, Bowen Lu, Yanhua Wu, Jing Wang, Xiaochun Li, Deguan Meng, Aimin Fan, Feiyue Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title | Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title_full | Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title_fullStr | Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title_full_unstemmed | Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title_short | Potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
title_sort | potential role of senescent macrophages in radiation-induced pulmonary fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141056/ https://www.ncbi.nlm.nih.gov/pubmed/34023858 http://dx.doi.org/10.1038/s41419-021-03811-8 |
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