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

IF 2.3 4区医学 Q3 PHARMACOLOGY & PHARMACY

Dose-Response Pub Date : 2025-06-20 eCollection Date: 2025-04-01 DOI:10.1177/15593258251352726

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

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引用次数: 0

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 in vivo and in vitro 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.

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nedd4介导的内皮-间质转化通过ATM信号通路参与辐射诱导的肺损伤

目的：鉴于EndMT在辐射肺损伤（RILI）发病机制中的调控途径尚不明确，阐明NEDD4在电离辐射（IR）诱导的内皮-间质转化（EndMT）中的作用及其分子机制。方法：采用免疫组化染色和Western blot方法，观察ir诱导的细胞内、外末端mt。通过RNA测序（RNA-seq）和定量实时聚合酶链反应（qRT-PCR），蛋白质组学鉴定出NEDD4为候选基因。京都基因与基因组百科（KEGG）通路分析将NEDD4与PI3K-AKT信号通路联系起来。共免疫沉淀（Co-IP）证实了NEDD4-ATM的相互作用。结果：IR上调内皮细胞中的NEDD4，与EndMT进展相关。NEDD4过表达增强ATM通路激活，调控ATM上下游基因。Co-IP验证了物理NEDD4-ATM绑定，表明NEDD4稳定了ATM，促进了EndMT。结论：总的来说，我们的研究表明NEDD4通过ATM信号通路介导EndMT参与RILI，这可能为了解RILI的发生和发展开辟了新的领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

4.90

自引率

4.00%

发文量

140

审稿时长

>12 weeks

期刊介绍： Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.