ArticleAmerican journal of respiratory cell and molecular biology2016
Toll-Like Receptor 4 Engagement Mediates Prolyl Endopeptidase Release from Airway Epithelia via Exosomes.
Article in American journal of respiratory cell and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 67 citations in OpenAlex.
- Proteolytic activities of extracellular vesicles attenuate A-synuclein aggregation.NPJ Parkinson's disease · 2025Article
- Adipose-derived stem cell exosomes: mechanisms and therapeutic potentials in wound healing.Biomarker research · 2025Review
- The Role of the Tumor Microenvironment (TME) in Advancing Cancer Therapies: Immune System Interactions, Tumor-Infiltrating Lymphocytes (TILs), and the Role of Exosomes and Inflammasomes.International journal of molecular sciences · 2025Review
- Serum Exosomes miR-122-5P Induces Hepatic and Renal Injury in Septic Rats by Regulating TAK1/SIRT1 Pathway.Infection and drug resistance · 2025Article
- Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis.iScience · 2024Article
- Extracellular vesicles in sputum of children with cystic fibrosis pulmonary exacerbations.ERJ open research · 2024Article
- Extracellular Vesicle-Associated Neutrophil Elastase Activates Hepatic Stellate Cells and Promotes Liver Fibrogenesis via ERK1/2 Pathway.bioRxiv : the preprint server for biology · 2024Article
- Exosome-encapsulated lncRNA HOTAIRM1 contributes to PMScience China. Life sciences · 2024Article
- Therapeutic Effect of Prolyl Endopeptidase Inhibitor in High-fat Diet-induced Metabolic Dysfunction-associated Fatty Liver Disease.Journal of clinical and translational hepatology · 2023Article
- Replenishing decoy extracellular vesicles inhibits phenotype remodeling of tissue-resident cells in inflammation-driven arthritis.Cell reports. Medicine · 2023Article
- Prolyl oligopeptidase inhibition ameliorates experimental pulmonary fibrosis both in vivo and in vitro.Respiratory research · 2023Article
- Morphologically intact airways in lung fibrosis have an abnormal proteome.Respiratory research · 2023Article
- Do Circulating Extracellular Vesicles Strictly Reflect Bronchoalveolar Lavage Extracellular Vesicles in COPD?International journal of molecular sciences · 2023Article
- Extracellular Vesicles' Role in the Pathophysiology and as Biomarkers in Cystic Fibrosis and COPD.International journal of molecular sciences · 2022Review
- Role of extracellular vesicles in severe pneumonia and sepsis.Expert opinion on biological therapy · 2022Review
- Extracellular Vesicles as Central Mediators of COPD Pathophysiology.Annual review of physiology · 2022Review
- An in vivo model for extracellular vesicle-induced emphysema.JCI insight · 2022Article
- Roles of exosomes and exosome-derived miRNAs in pulmonary fibrosis.Frontiers in pharmacology · 2022Review
- Extracellular vesicles: mediators of intercellular communication in tissue injury and disease.Cell communication and signaling : CCS · 2021Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Proteases are important regulators of pulmonary remodeling and airway inflammation. Recently, we have characterized the enzyme prolyl endopeptidase (PE), a serine peptidase, as a critical protease in the generation of the neutrophil chemoattractant tripeptide Pro-Gly-Pro (PGP) from collagen. However, PE has been characterized as a cytosolic enzyme, and the mechanism mediating PE release extracellularly remains unknown. We examined the role of exosomes derived from airway epithelia as a mechanism for PE release and the potential extracellular signals that regulate the release of these exosomes. We demonstrate a specific regulatory pathway of exosome release from airway epithelia and identify PE as novel exosome cargo. LPS stimulation of airway epithelial cells induces release of PE-containing exosomes, which is significantly attenuated by small interfering RNA depletion of Toll-like receptor 4 (TLR4). These differences were recapitulated upon intratracheal LPS administration in mice competent versus deficient for TLR4 signaling. Finally, sputum samples from subjects with cystic fibrosis colonized with Pseudomonas aeruginosa demonstrate elevated exosome content and increased PE levels. This TLR4-based mechanism highlights the first report of nonstochastic release of exosomes in the lung and couples TLR4 activation with matrikine generation. The increased quantity of these proteolytic exosomes in the airways of subjects with chronic lung disease highlights a new mechanism of injury and inflammation in the pathogenesis of pulmonary disorders.
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.