ArticlePloS one2012
Evolutionary conserved role of c-Jun-N-terminal kinase in CO2-induced epithelial dysfunction.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 46 citations in OpenAlex.
- Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial.Metabolites · 2026Article
- Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review.International journal of molecular sciences · 2025Article
- Sensing molecular carbon dioxide: a translational focus for respiratory disease.Physiological reviews · 2025Review
- Optimizing Mechanical Ventilation Strategies in ARDS: The Role of Driving Pressure and Low Tidal Volume Ventilation.Critical care research and practice · 2025Review
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- In Search of a Sensor: How Does COAmerican journal of respiratory cell and molecular biology · 2021Article
- Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease.The Journal of membrane biology · 2021Article
- Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Elevated COInterface focus · 2021Review
- Carbon dioxide-dependent signal transduction in mammalian systems.Interface focus · 2021Review
- Mechanisms of Hypercapnia-Induced Endoplasmic Reticulum Dysfunction.Frontiers in physiology · 2021Review
- TRAF2 Is a Novel Ubiquitin E3 Ligase for the Na,K-ATPase β-Subunit That Drives Alveolar Epithelial Dysfunction in Hypercapnia.Frontiers in cell and developmental biology · 2021Article
- Hypercapnia: An Aggravating Factor in Asthma.Journal of clinical medicine · 2020Review
- High COAmerican journal of respiratory cell and molecular biology · 2020Article
- The role of carbon dioxide in nematode behaviour and physiology.Parasitology · 2020Review
- Hypercapnia Impairs Na,K-ATPase Function by Inducing Endoplasmic Reticulum Retention of the β-Subunit of the Enzyme in Alveolar Epithelial Cells.International journal of molecular sciences · 2020Article
- Hypercapnia Regulates Gene Expression and Tissue Function.Frontiers in physiology · 2020Review
- Elevated COScientific reports · 2019Article
- Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Intrinsic JNK-MAPK pathway involvement requires daf-16-mediated immune response during Shigella flexneri infection in C. elegans.Immunologic research · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
Abstract
Elevated CO(2) levels (hypercapnia) occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK) in CO(2) signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO(2) levels rapidly induced activation of JNK leading to downregulation of Na,K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK) and protein kinase C-ζ leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO(2) levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO(2)-induced downregulation of Na,K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO(2) signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO(2) signaling in mammals, diptera and nematodes.
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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.