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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...

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Autores principales: Su, Lulu, Dong, Yinping, Wang, Yueying, Wang, Yuquan, Guan, Bowen, Lu, Yanhua, Wu, Jing, Wang, Xiaochun, Li, Deguan, Meng, Aimin, Fan, Feiyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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