Trial reportThe Journal of biological chemistry2012
Hyaluronan and layilin mediate loss of airway epithelial barrier function induced by cigarette smoke by decreasing E-cadherin.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 81 citations in OpenAlex.
- Hyaluronan Signaling Ameliorates the Epithelial Injury Response and Barrier Disruption After Ozone Exposure.Biomolecules · 2026Article
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.PLoS pathogens · 2026Article
- Article
- Layilin at the crossroads of immunity and motility: a C-type lectin receptor in Hyaluronan Signaling.Glycobiology · 2025Review
- The hyaluronan receptor CD44 drives COVID-19 severity through its regulation of neutrophil migration.bioRxiv : the preprint server for biology · 2025Article
- Layilin: a multifunctional hyaluronan receptor in physiology and pathology.Frontiers in oncology · 2025Review
- The Bidirectional Gut-Lung Axis in Chronic Obstructive Pulmonary Disease.American journal of respiratory and critical care medicine · 2023Review
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Loss of E-cadherin is causal to pathologic changes in chronic lung disease.Communications biology · 2022Article
- Proteoglycans in Toll-like receptor responses and innate immunity.American journal of physiology. Cell physiology · 2022Review
- The role of hyaluronan synthesis and degradation in the critical respiratory illness COVID-19.American journal of physiology. Cell physiology · 2022Review
- Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties.Stem cell research & therapy · 2022Review
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.Molecules (Basel, Switzerland) · 2022Article
- Current views in chronic obstructive pulmonary disease pathogenesis and management.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021Review
- Blocking hyaluronan synthesis alleviates acute lung allograft rejection.JCI insight · 2021Article
- COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction.JCI insight · 2021Article
- Effects of ozone and particulate matter on airway epithelial barrier structure and function: a review ofInhalation toxicology · 2021Review
- Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells-overview and perspectives.In vitro cellular & developmental biology. Animal · 2021Review
- E-Cadherin: An Important Functional Molecule at Respiratory Barrier Between Defence and Dysfunction.Frontiers in physiology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Cigarette smoke (CigS) exposure is associated with increased bronchial epithelial permeability and impaired barrier function. Primary cultures of normal human bronchial epithelial cells exposed to CigS exhibit decreased E-cadherin expression and reduced transepithelial electrical resistance. These effects were mediated by hyaluronan (HA) because inhibition of its synthesis with 4-methylumbelliferone prevented these effects, and exposure to HA fragments of <70 kDa mimicked these effects. We show that the HA receptor layilin is expressed apically in human airway epithelium and that cells infected with lentivirus expressing layilin siRNAs were protected against increased permeability triggered by both CigS and HA. We identified RhoA/Rho-associated protein kinase (ROCK) as the signaling effectors downstream layilin. We conclude that HA fragments generated by CigS bind to layilin and signal through Rho/ROCK to inhibit the E-cadherin gene and protein expression, leading to a loss of epithelial cell-cell contact. These studies suggest that HA functions as a master switch protecting or disrupting the epithelial barrier in its high versus low molecular weight form and that its depolymerization is a first and necessary step triggering the inflammatory response to CigS.
Indexed as
Identifiers
What OpenQuestion holds
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.