ArticleThe American journal of pathology2017
p53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis.
Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 112 citations in OpenAlex.
- The Role of MicroRNAs Implicated in the Regulation of PI3K/AKT and Focal Adhesion Signaling Pathways in Chronic Obstructive Pulmonary Disease.Biochemical genetics · 2026Article
- Emerging therapeutic potential of umbilical cord-derived extracellular vesicles in lung-injurious diseases: a review of recent advances.Stem cell research & therapy · 2026Review
- Therapeutic Potential of Lentiviral miR-200a Mimics in Regulating Fibrinolysis and EMT Markers During Pulmonary Fibrosis.FASEB bioAdvances · 2026Article
- Interleukin-17A Orchestrates Lung Injury and Remodeling Through p53 and uPA System Crosstalk.International journal of molecular sciences · 2026Article
- Shikonin treatment ameliorates lipopolysaccharide-induced acute liver failure in mice via regulating miR-106/MCL1 and miR-34a/SIRT1/TP53 signaling.Archives of medical science : AMS · 2026Article
- 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
- Fungal protein D1 inhibits the proliferation of A549 cells via activating the p53/miR-34a signaling pathway.Journal of natural medicines · 2025Article
- Portal Fibrosis and the Ductular Reaction: Pathophysiological Role in the Progression of Liver Disease and Translational Opportunities.Gastroenterology · 2025Review
- Ratio of miRNA-29 to miRNA-199 expression coordinates mesenchymal stem cell repair of bleomycin-induced pulmonary injury.Molecular therapy. Nucleic acids · 2025Article
- PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy.Communications biology · 2025Article
- Epigenetic regulation of histone 3 acetylation and p53 by SIRT1 overexpression in an experimental model of alveolar epithelium damage.Journal of biosciences · 2025Article
- p53 and the E3 Ubiquitin Ligase MDM2 in Glaucomatous Lamina Cribrosa Cells.International journal of molecular sciences · 2024Article
- Emerging roles of senolytics/senomorphics in HIV-related co-morbidities.Biochemical pharmacology · 2024Review
- Epithelial-mesenchymal transition in tissue repair and degeneration.Nature reviews. Molecular cell biology · 2024Review
- Targeting tumor suppressor p53 for organ fibrosis therapy.Cell death & disease · 2024Review
- Microarray analysis of microrna expression in peripheral blood mononuclear cells of patients with polymyositis and dermatomyositis.Journal of translational internal medicine · 2024Article
- The role and regulation of SIRT1 in pulmonary fibrosis.Molecular biology reports · 2024Review
- The Roles of MicroRNAs in Asthma and Emerging Insights into the Effects of Vitamin DNutrients · 2024Review
- Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway.Open medicine (Warsaw, Poland) · 2024Article
- FOXO4-D-Retro-Inverso targets extracellular matrix production in fibroblasts and ameliorates bleomycin-induced pulmonary fibrosis in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. The pathogenesis of interstitial lung diseases, including its most common form, IPF, remains poorly understood. Alveolar epithelial cell (AEC) apoptosis, proliferation, and accumulation of myofibroblasts and extracellular matrix deposition results in progressive loss of lung function in IPF. We found induction of tumor suppressor protein, p53, and apoptosis with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients, and in mice with bleomycin, cigarette smoke, silica, or sepsis-induced lung injury. Treatment with the caveolin-1 scaffolding domain peptide (CSP) reversed these effects. Consistent with induction of p53, AECs from IPF lungs or mice with diverse types of lung injuries showed increased p53 acetylation and miR-34a expression with reduction in Sirt1. This was significantly reduced after treatment of wild-type mice with CSP, and uPA-deficient mice were unresponsive. Bleomycin failed to induce miR-34a in p53- or plasminogen activator inhibitor-1 (PAI-1)-deficient mice. CSP-mediated inhibition of miR-34a restored Sirt1, suppressed p53 acetylation and apoptosis in injured AECs, and prevented pulmonary fibrosis (PF). AEC-specific suppression of miR-34a inhibited bleomycin-induced p53, PAI-1, and apoptosis and prevented PF, whereas overexpression of precursor-miR-34a increased p53, PAI-1, and apoptosis in AECs of mice unexposed to bleomycin. Our study validates p53-miR-34a feedback as a potential therapeutic target in PF.
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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.