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Updated: Sep 18, 2025
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
NEDD4-Mediated Endothelial-Mesenchymal Transition Participates in Radiation-Induced Lung Injury Through the ATM
Yang Feng1,2, Lirong Zhang1, Youbin Zhang3
1State 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.
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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