Cargando…

Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells

The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Lu-Kai, Wu, Tsai-Jung, Hong, Ji-Hong, Chen, Fang-Hsin, Yu, John, Wang, Chun-Chieh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542528/
https://www.ncbi.nlm.nih.gov/pubmed/33061990
http://dx.doi.org/10.1155/2020/6312053
_version_ 1783591569464492032
author Wang, Lu-Kai
Wu, Tsai-Jung
Hong, Ji-Hong
Chen, Fang-Hsin
Yu, John
Wang, Chun-Chieh
author_facet Wang, Lu-Kai
Wu, Tsai-Jung
Hong, Ji-Hong
Chen, Fang-Hsin
Yu, John
Wang, Chun-Chieh
author_sort Wang, Lu-Kai
collection PubMed
description The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis.
format Online
Article
Text
id pubmed-7542528
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-75425282020-10-13 Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells Wang, Lu-Kai Wu, Tsai-Jung Hong, Ji-Hong Chen, Fang-Hsin Yu, John Wang, Chun-Chieh Stem Cells Int Research Article The lung is a radiosensitive organ, which imposes limits on the therapeutic dose in thoracic radiotherapy. Irradiated alveolar epithelial cells promote radiation-related pneumonitis and fibrosis. However, the role of lung stem cells (LSCs) in the development of radiation-induced lung injury is still unclear. In this study, we found that both LSCs and LSC-derived type II alveolar epithelial cells (AECII) can repair radiation-induced DNA double-strand breaks, but the irradiated LSCs underwent growth arrest and cell differentiation faster than the irradiated AECII cells. Moreover, radiation drove LSCs to fibrosis as shown with the elevated levels of markers for epithelial-mesenchymal transition and myofibroblast (α-smooth muscle actin (α-SMA)) differentiation in in vitro and ex vivo studies. Increased gene expressions of connective tissue growth factor and α-SMA were found in both irradiated LSCs and alveolar cells, suggesting that radiation could induce the fibrogenic differentiation of LSCs. Irradiated LSCs showed an increase in the expression of surfactant protein C (SP-C), the AECII cell marker, and α-SMA, and irradiated AECII cells expressed SP-C and α-SMA. These results indicated that radiation induced LSCs to differentiate into myofibroblasts and AECII cells; then, AECII cells differentiated further into either myofibroblasts or type I alveolar epithelial cells (AECI). In conclusion, our results revealed that LSCs are sensitive to radiation-induced cell damage and may be involved in radiation-induced lung fibrosis. Hindawi 2020-09-29 /pmc/articles/PMC7542528/ /pubmed/33061990 http://dx.doi.org/10.1155/2020/6312053 Text en Copyright © 2020 Lu-Kai Wang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wang, Lu-Kai
Wu, Tsai-Jung
Hong, Ji-Hong
Chen, Fang-Hsin
Yu, John
Wang, Chun-Chieh
Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title_full Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title_fullStr Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title_full_unstemmed Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title_short Radiation Induces Pulmonary Fibrosis by Promoting the Fibrogenic Differentiation of Alveolar Stem Cells
title_sort radiation induces pulmonary fibrosis by promoting the fibrogenic differentiation of alveolar stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542528/
https://www.ncbi.nlm.nih.gov/pubmed/33061990
http://dx.doi.org/10.1155/2020/6312053
work_keys_str_mv AT wanglukai radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells
AT wutsaijung radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells
AT hongjihong radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells
AT chenfanghsin radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells
AT yujohn radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells
AT wangchunchieh radiationinducespulmonaryfibrosisbypromotingthefibrogenicdifferentiationofalveolarstemcells