{"title":"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","authors":"Yang Feng, Lirong Zhang, Youbin Zhang, Ying Xu, Kaixiao Zhou, Zhao Yang, Wei Zhu, Qi Zhang, Jianping Cao, Lili Wang, Yang Jiao","doi":"10.1177/15593258251352726","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>IR-induced EndMT was observed during RILI <i>in</i> <i>vivo</i> and <i>in</i> <i>vitro</i> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11285,"journal":{"name":"Dose-Response","volume":"23 2","pages":"15593258251352726"},"PeriodicalIF":2.3000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181723/pdf/","citationCount":"0","resultStr":"{\"title\":\"NEDD4-Mediated Endothelial-Mesenchymal Transition Participates in Radiation-Induced Lung Injury Through the ATM Signaling Pathway.\",\"authors\":\"Yang Feng, Lirong Zhang, Youbin Zhang, Ying Xu, Kaixiao Zhou, Zhao Yang, Wei Zhu, Qi Zhang, Jianping Cao, Lili Wang, Yang Jiao\",\"doi\":\"10.1177/15593258251352726\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>IR-induced EndMT was observed during RILI <i>in</i> <i>vivo</i> and <i>in</i> <i>vitro</i> 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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":11285,\"journal\":{\"name\":\"Dose-Response\",\"volume\":\"23 2\",\"pages\":\"15593258251352726\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181723/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Dose-Response\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/15593258251352726\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dose-Response","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/15593258251352726","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
NEDD4-Mediated Endothelial-Mesenchymal Transition Participates in Radiation-Induced Lung Injury Through the ATM Signaling Pathway.
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 invivo and invitro 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.
Dose-ResponsePHARMACOLOGY & 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.
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