NEDD4介导的内皮-间充质转化通过ATM信号通路参与放射性肺损伤。

NEDD4-Mediated Endothelial-Mesenchymal Transition Participates in Radiation-Induced Lung Injury Through the ATM Signaling Pathway.

作者信息

Feng Yang, Zhang Lirong, Zhang Youbin, Xu Ying, Zhou Kaixiao, Yang Zhao, Zhu Wei, Zhang Qi, Cao Jianping, Wang Lili, Jiao Yang

机构信息

State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Key Laboratory of Radiation Damage and Treatment of Jiangsu Provincial Universities and Colleges, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China.

Department of Oncology, Wuxi No. 2 People's Hospital, Jiangnan University Medical Center, Wuxi, China.

出版信息

Dose Response. 2025 Jun 20;23(2):15593258251352726. doi: 10.1177/15593258251352726. eCollection 2025 Apr-Jun.

DOI:10.1177/15593258251352726

PMID:40548124

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12181723/

Abstract

OBJECTIVE

To elucidate the role of NEDD4 in ionizing radiation (IR)-induced endothelial-mesenchymal transition (EndMT) and its molecular mechanism in radiation-induced lung injury (RILI), given the unclear regulatory pathways of EndMT in RILI pathogenesis.

METHODS

IR-induced EndMT was observed during RILI and by immunohistochemical staining and Western blot analysis. Proteomics identified NEDD4 as a candidate, validated by RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT‒PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis linked NEDD4 to PI3K-AKT signaling. Co-immunoprecipitation (Co-IP) confirmed NEDD4-ATM interaction.

RESULTS

IR upregulated NEDD4 in endothelial cells, correlating with EndMT progression. NEDD4 overexpression enhanced ATM pathway activation, modulating genes upstream/downstream of ATM. Co-IP verified physical NEDD4-ATM binding, suggesting NEDD4 stabilizes ATM to promote EndMT.

CONCLUSION

Overall, our study shows that NEDD4 mediates EndMT to participate in RILI through the ATM signaling pathway, which may break new ground for understanding the occurrence and development of RILI.

摘要

目的

鉴于在放射性肺损伤（RILI）发病机制中内皮-间质转化（EndMT）的调控途径尚不清楚，本研究旨在阐明NEDD4在电离辐射（IR）诱导的EndMT中的作用及其在RILI中的分子机制。

方法

在RILI过程中，通过免疫组织化学染色和蛋白质印迹分析观察IR诱导的EndMT。蛋白质组学将NEDD4鉴定为候选蛋白，并通过RNA测序（RNA-seq）和定量实时聚合酶链反应（qRT-PCR）进行验证。京都基因与基因组百科全书（KEGG）通路分析将NEDD4与PI3K-AKT信号通路联系起来。免疫共沉淀（Co-IP）证实了NEDD4与ATM的相互作用。