ArticleBritish journal of pharmacology2020
Plasmin improves blood-gas barrier function in oedematous lungs by cleaving epithelial sodium channels.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Epithelial Sodium Channel in the Respiratory System: A Bibliometric Review of Recent Studies.Biology · 2026Review
- Double-edged sword: flavivirus NS1 enhances human plasmin-mediated fibrinolysis while being targeted for cleavage and inactivation.The Journal of general virology · 2026Article
- Liposome-Based Nanoparticle Delivery Systems for Lung Diseases: Opportunities and Challenges.International journal of nanomedicine · 2025Review
- Mechanisms influencing the high prevalence of COVID-19 in diabetics: A systematic review.Medical research archives · 2023Article
- PAI-1 regulates AT2-mediated re-alveolarization and ion permeability.Stem cell research & therapy · 2023Article
- Fibrinolytic system and COVID-19: From an innovative view of epithelial ion transport.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Regulation of Epithelial Sodium Transport by SARS-CoV-2 Is Closely Related with Fibrinolytic System-Associated Proteins.Biomolecules · 2023Review
- PAI-1 regulates AT2-mediated re-alveolarization and ion permeability.Research square · 2023Article
- Competitive cleavage of SARS-CoV-2 spike protein and epithelial sodium channel by plasmin as a potential mechanism for COVID-19 infection.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit.The Journal of biological chemistry · 2022Article
- Fibrinolytic or anti-plasmin (nafamostat) therapy for COVID-19: A timing challenge for clinicians.Pulmonary pharmacology & therapeutics · 2021Article
- Fibrinolytic niche is required for alveolar type 2 cell-mediated alveologenesis via a uPA-A6-CD44Signal transduction and targeted therapy · 2021Article
- Osmotic Adaptation by NaBiomedicines · 2020Review
- Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics?Biomolecules · 2020Review
- Plasmin improves blood-gas barrier function in oedematous lungs by cleaving epithelial sodium channels.British journal of pharmacology · 2020Article
- Elevated Plasmin(ogen) as a Common Risk Factor for COVID-19 Susceptibility.Physiological reviews · 2020Review
- Molecular Aspects of Co-morbidities in COVID-19 Infection.The archives of bone and joint surgery · 2020Review
- COVID-19-Associated Hyper-Fibrinolysis: Mechanism and Implementations.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
background and purposeLung oedema in association with suppressed fibrinolysis is a hallmark of lung injury. Here, we have tested whether plasmin cleaves epithelial sodium channels (ENaC) to resolve lung oedema fluid. EXPERIMENTAL APPROACH: Human lungs and airway acid-instilled mice were used for analysing fluid resolution. In silico prediction, mutagenesis, Xenopus oocytes, immunoblotting, voltage clamp, mass spectrometry, and protein docking were combined for identifying plasmin cleavage sites. KEY
resultsPlasmin improved lung fluid resolution in both human lungs ex vivo and injured mice. Plasmin activated αβγENaC channels in oocytes in a time-dependent manner. Deletion of four consensus proteolysis tracts (αΔ432-444, γΔ131-138, γΔ178-193, and γΔ410-422) eliminated plasmin-induced activation significantly. Further, immunoblotting assays identified 7 cleavage sites (K126, R135, K136, R153, K168, R178, K179) for plasmin to trim both furin-cleaved C-terminal fragments and full-length human γENaC proteins. In addition, 9 new sites (R122, R137, R138, K150, K170, R172, R180, K181, K189) in synthesized peptides were found to be cleaved by plasmin. These cleavage sites were located in the finger and the thumb, particularly the GRIP domain of human ENaC 3D model composed of two proteolytic centres for plasmin. Novel uncleaved sites beyond the GRIP domain in both α and γ subunits were identified to interrupt the plasmin cleavage-induced conformational change in ENaC channel complexes. Additionally, plasmin could regulate ENaC activity via the G protein signal. CONCLUSION AND IMPLICATIONS: Plasmin can cleave ENaC to improve blood-gas exchange by resolving oedema fluid and could be a potent therapy for oedematous lungs.
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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.