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Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling
Radiation-induced lung injury is a common late side effect of thoracic radiotherapy. Endothelial dysfunction following leukocytes infiltration is a prominent feature in this process. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found the activity of phos...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859005/ https://www.ncbi.nlm.nih.gov/pubmed/35243230 http://dx.doi.org/10.1016/j.isci.2022.103867 |
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author | Liu, Pan Li, Yiqing Li, Mengyao Zhou, Hui Zhang, Huilun Zhang, Yuefei Xu, Jiaqi Xu, Yun Zhang, Jie Xia, Bing Cheng, Hongqiang Ke, Yuehai Zhang, Xue |
author_facet | Liu, Pan Li, Yiqing Li, Mengyao Zhou, Hui Zhang, Huilun Zhang, Yuefei Xu, Jiaqi Xu, Yun Zhang, Jie Xia, Bing Cheng, Hongqiang Ke, Yuehai Zhang, Xue |
author_sort | Liu, Pan |
collection | PubMed |
description | Radiation-induced lung injury is a common late side effect of thoracic radiotherapy. Endothelial dysfunction following leukocytes infiltration is a prominent feature in this process. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found the activity of phosphatase Shp2 was elevated in endothelium after injury. Endothelium-specific Shp2 deletion mice showed relieved collagen deposition along with disrupted radiation-induced Jag1 expression in the endothelium. Furthermore, endothelium-derived Jag1 activated the alternative activation of macrophages in vitro and in vivo by paracrine Notch signaling. Consistently, the Notch pathway was significantly activated by chest irradiation in the peripheral blood leukocytes of patients with cancer. Collectively, our work demonstrates that Shp2 participates in the radiation-induced endothelial dysfunction and subsequently inflammatory microenvironment producing during radiation-induced lung injury. Our findings indicate Shp2 as a potential target for radiation-induced lung injury and provide another way for endothelium to participate in the pathological process of radiation-induced lung injury. |
format | Online Article Text |
id | pubmed-8859005 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88590052022-03-02 Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling Liu, Pan Li, Yiqing Li, Mengyao Zhou, Hui Zhang, Huilun Zhang, Yuefei Xu, Jiaqi Xu, Yun Zhang, Jie Xia, Bing Cheng, Hongqiang Ke, Yuehai Zhang, Xue iScience Article Radiation-induced lung injury is a common late side effect of thoracic radiotherapy. Endothelial dysfunction following leukocytes infiltration is a prominent feature in this process. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found the activity of phosphatase Shp2 was elevated in endothelium after injury. Endothelium-specific Shp2 deletion mice showed relieved collagen deposition along with disrupted radiation-induced Jag1 expression in the endothelium. Furthermore, endothelium-derived Jag1 activated the alternative activation of macrophages in vitro and in vivo by paracrine Notch signaling. Consistently, the Notch pathway was significantly activated by chest irradiation in the peripheral blood leukocytes of patients with cancer. Collectively, our work demonstrates that Shp2 participates in the radiation-induced endothelial dysfunction and subsequently inflammatory microenvironment producing during radiation-induced lung injury. Our findings indicate Shp2 as a potential target for radiation-induced lung injury and provide another way for endothelium to participate in the pathological process of radiation-induced lung injury. Elsevier 2022-02-05 /pmc/articles/PMC8859005/ /pubmed/35243230 http://dx.doi.org/10.1016/j.isci.2022.103867 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Liu, Pan Li, Yiqing Li, Mengyao Zhou, Hui Zhang, Huilun Zhang, Yuefei Xu, Jiaqi Xu, Yun Zhang, Jie Xia, Bing Cheng, Hongqiang Ke, Yuehai Zhang, Xue Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title | Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title_full | Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title_fullStr | Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title_full_unstemmed | Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title_short | Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
title_sort | endothelial shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859005/ https://www.ncbi.nlm.nih.gov/pubmed/35243230 http://dx.doi.org/10.1016/j.isci.2022.103867 |
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