Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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
_version_ 1784654357740912640
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
work_keys_str_mv AT liupan endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT liyiqing endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT limengyao endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT zhouhui endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT zhanghuilun endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT zhangyuefei endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT xujiaqi endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT xuyun endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT zhangjie endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT xiabing endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT chenghongqiang endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT keyuehai endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling
AT zhangxue endothelialshp2deficiencycontrolsalternativeactivationofmacrophagepreventingradiationinducedlunginjurythroughnotchsignaling