ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
Regulation of p53-mediated changes in the uPA-fibrinolytic system and in lung injury by loss of surfactant protein C expression in alveolar epithelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19.Scientific reports · 2024Trial
- Interleukin-17A Orchestrates Lung Injury and Remodeling Through p53 and uPA System Crosstalk.International journal of molecular sciences · 2026Article
- Deciphering Oxidative Stress in Cardiovascular Disease Progression: A Blueprint for Mechanistic Understanding and Therapeutic Innovation.Antioxidants (Basel, Switzerland) · 2024Review
- Transcriptomic analysis of profibrinolytic and fibrinolytic inhibitor genes in COVID-19 patients.Narra J · 2024Article
- LncRNA HOTTIP promotes LPS-induced lung epithelial cell injury by recruiting DNMT1 to epigenetically regulate SP-C.Journal of cell communication and signaling · 2024Article
- The critical roles of caveolin-1 in lung diseases.Frontiers in pharmacology · 2024Review
- Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury.International journal of molecular sciences · 2023Article
- Molecular Impact of Conventional and Electronic Cigarettes on Pulmonary Surfactant.International journal of molecular sciences · 2023Review
- Review
- Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice.PloS one · 2023Article
- Article
- Review
- An Update on COVID-19 Vaccine Induced Thrombotic Thrombocytopenia Syndrome and Some Management Recommendations.Molecules (Basel, Switzerland) · 2021Review
- The Central Role of Fibrinolytic Response in COVID-19-A Hematologist's Perspective.International journal of molecular sciences · 2021Review
- P53 in the impaired lungs.DNA repair · 2020Review
- Two distinct immunopathological profiles in autopsy lungs of COVID-19.Nature communications · 2020Article
- Acute Lung Injury: IL-17A-Mediated Inflammatory Pathway and Its Regulation by Curcumin.Inflammation · 2019Review
- The Cardioprotective Signaling Activity of Activated Protein C in Heart Failure and Ischemic Heart Diseases.International journal of molecular sciences · 2019Review
- p53 Expression in Lung Fibroblasts Is Linked to Mitigation of Fibrotic Lung Remodeling.The American journal of pathology · 2018Article
- Potential contribution of alveolar epithelial type I cells to pulmonary fibrosis.Bioscience reports · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary surfactant protein C (SP-C) expression by type II alveolar epithelial cells (AECs) is markedly reduced in diverse types of lung injuries and is often associated with AEC apoptosis. It is unclear whether loss of SP-C contributes to the increased p53 and urokinase-type plasminogen activator (uPA) system cross-talk and apoptosis of AECs. Therefore, we inhibited SP-C expression in human and murine AECs using lentivirus vector expressing shRNA and tested p53 and downstream changes in the uPA-fibrinolytic system. Inhibition of SP-C expression in AECs induced p53 and activated caspase-3, indicating AEC apoptosis. We also found that bleomycin or cigarette smoke exposure failed to inhibit SP-C expression or apoptosis in AECs in p53- and plasminogen activator inhibitor-1 (PAI-1)-deficient mice. Depletion of SP-C expression by lentiviral SP-C shRNA in PAI-1-deficient mice failed to induce p53 or apoptosis in AECs, whereas it increased both AEC p53 and apoptosis in wild-type and uPA-deficient mice. SP-C inhibition in AECs also increased in CXCL1 and CXCL2 and their receptor CXCR2 as well as ICAM-1 expression, which is indicative of a proinflammatory response. Overexpression of p53-binding 3'-UTR sequences in AECs inhibited PAI-1 induction while maintaining uPA and uPAR protein and mRNA expression. Furthermore, caveolin-1 expression and phosphorylation were increased in AECs, indicating an intricate link between caveolin-1 and Src kinase-mediated cell signaling and AEC apoptosis due to loss of SP-C expression through p53 and uPA system-mediated cross-talk. The role of uPA, PAI-1, and p53 in the regulation of AEC apoptosis after injury was also determined in knockout mice.
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Registered trials
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