ArticleJCI insight2019
DNA replication in progenitor cells and epithelial regeneration after lung injury requires the oncoprotein MDM2.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Phosgene-Induced acute lung injury: Approaches for mechanism-based treatment strategies.Frontiers in immunology · 2022Pooled it
- Lactic Acid Drives ESM1 to Attenuate DNA Damage and CD8+ T Cell Infiltration in Cancer.Oncology research · 2026Article
- The Impact of METTL3 on MDM2 Promotes Podocytes Injury During Diabetic Kidney Disease.Journal of cellular and molecular medicine · 2025Article
- Ursolic Acid Alleviates Mitotic Catastrophe in Podocyte by Inhibiting Autophagic P62 Accumulation in Diabetic Nephropathy.International journal of biological sciences · 2024Article
- Pulmonary endogenous progenitor stem cell subpopulation: Physiology, pathogenesis, and progress.Journal of intensive medicine · 2023Review
- Tolerogenic dendritic cells in radiation-induced lung injury.Frontiers in immunology · 2023Review
- Promising Biomarkers of Radiation-Induced Lung Injury: A Review.Biomedicines · 2021Review
- Disrupting biological sensors of force promotes tissue regeneration in large organisms.Nature communications · 2021Article
- Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- The oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3.Nature communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Depletion of epithelial cells after lung injury prompts proliferation and epithelial mesenchymal transition (EMT) of progenitor cells, and this repopulates the lost epithelial layer. To investigate the cell proliferative function of human oncoprotein MDM2, we generated mouse models targeting human MDM2 expression in either lung Club or alveolar cells after doxycycline treatment. We report that MDM2 expression in lung Club or alveolar cells activates DNA replication specifically in lung progenitor cells only after chemical- or radiation-induced lung injury, irrespective of their p53 status. Activation of DNA replication by MDM2 triggered by injury leads to proliferation of lung progenitor cells and restoration of the lost epithelial layers. Mouse lung with no Mdm2 allele loses its ability to replicate DNA, whereas loss of 1 Mdm2 allele compromises this function, demonstrating the requirement of endogenous MDM2. We show that the p53-independent ability of MDM2 to activate Akt signaling is essential for initiating DNA replication in lung progenitor cells. Furthermore, MDM2 activates the Notch signaling pathway and expression of EMT markers, indicative of epithelial regeneration. This is the first report to our knowledge demonstrating a direct p53-independent participation of MDM2 in progenitor cell proliferation and epithelial repair after lung injury, distinct from a p53-degrading antiapoptotic effect preventing injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.