ArticleThe Journal of experimental medicine2021
Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 43 citations in OpenAlex.
- Hallmarks of the ageing lung: 10 years later.The European respiratory journal · 2026Review
- Myeloperoxidase promotes fibrosis by inhibiting cathepsin K to bias the lung toward ECM accumulation.bioRxiv : the preprint server for biology · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- p53-miR-34a feedback in lung fibroblasts regulates antifibrotic effects of CSP7, nintedanib, and pirfenidone.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Depletion of tropomyosin 1.6 alleviates TGF-β1-induced fibroblast activation by promoting the α-SMA-MMP9 matrix-degrading structure.iScience · 2025Article
- p53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells.International journal of molecular sciences · 2024Article
- A novel senolytic drug for pulmonary fibrosis: BTSA1 targets apoptosis of senescent myofibroblasts by activating BAX.Aging cell · 2024Article
- Cell Proliferation and Apoptosis-Key Players in the Lung Aging Process.International journal of molecular sciences · 2024Review
- Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis.Nature communications · 2024Article
- Targeting tumor suppressor p53 for organ fibrosis therapy.Cell death & disease · 2024Review
- Article
- Inhibitor of PD-1/PD-L1: a new approach may be beneficial for the treatment of idiopathic pulmonary fibrosis.Journal of translational medicine · 2024Review
- In vitro co-culture studies and the crucial role of fibroblast-immune cell crosstalk in IPF pathogenesis.Respiratory research · 2023Review
- Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets.Signal transduction and targeted therapy · 2023Review
- The lung mesenchyme in development, regeneration, and fibrosis.The Journal of clinical investigation · 2023Review
- Pulmonary fibrosis: A short- or long-term sequelae of severe COVID-19?Chinese medical journal pulmonary and critical care medicine · 2023Review
- Article
- Pharmacological inhibition of MDM4 alleviates pulmonary fibrosis.Theranostics · 2023Article
- Targeted delivery of ZNF416 siRNA-loaded liposomes attenuates experimental pulmonary fibrosis.Journal of translational medicine · 2022Article
- Stem cells, cell therapies, and bioengineering in lung biology and disease 2021.American journal of physiology. Lung cellular and molecular physiology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Aging is a strong risk factor and an independent prognostic factor for progressive human idiopathic pulmonary fibrosis (IPF). Aged mice develop nonresolving pulmonary fibrosis following lung injury. In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice. We identified MDM4 as a matrix stiffness-regulated endogenous inhibitor of p53. Reducing matrix stiffness down-regulates MDM4 expression, resulting in p53 activation in primary lung myofibroblasts isolated from IPF patients. Gain of p53 function activates a gene program that sensitizes lung myofibroblasts to apoptosis and promotes the clearance of apoptotic myofibroblasts by macrophages. Destiffening of the fibrotic lung matrix by targeting nonenzymatic cross-linking or genetic ablation of Mdm4 in lung (myo)fibroblasts activates the Mdm4-p53 pathway and promotes lung fibrosis resolution in aged mice. These findings suggest that mechanosensitive MDM4 is a molecular target with promising therapeutic potential against persistent lung fibrosis associated with aging.
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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.