ArticleJCI insight2018
Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 52 citations in OpenAlex.
- Pro-inflammatory and matricellular protein expression patterns associated with bronchopulmonary dysplasia severity.Pediatric research · 2026Article
- Immunomodulatory role and therapeutic potential of thrombospondin-1 during infectious diseases and autoimmunity.BMC biology · 2026Review
- Myeloid-derived interleukin-10 induced by thrombospondin-1 mediates host defense and regulates inflammation during acute bacterial lung infection.Infection and immunity · 2026Article
- Megakaryocyte and platelet thrombospondin-1 regulates matrix remodeling by stabilizing basement membrane COL6A1 in lung injury.Nature communications · 2026Article
- Unraveling the Matrix: Proteomic Profiling Reveals Stromal ECM Dysregulation in Severe Early-Onset Fetal Growth Restriction.International journal of molecular sciences · 2025Article
- GATA2 mutation is associated with immune dysfunction and increased Mycobacterium haemophilum susceptibility in immunocompromised individuals.JCI insight · 2025Article
- Macrophage-derived IL-1β directs fibroblast progenitor cell fate via metabolic reprogramming in wound healing.Communications biology · 2025Article
- Thrombospondin-1 Airway Expression and Thrombospondin-1 Gene Variants Are Associated with Bronchopulmonary Dysplasia in Extremely Low-Birth-Weight Infants: A Pilot Study.Children (Basel, Switzerland) · 2025Article
- Proteomic characterization of molecular mechanisms of paraquat-induced lung injury in a mouse model.Respiratory research · 2025Article
- The dual role of thrombospondin-1 in inflammatory regulation during acute respiratory distress syndrome: a mini-review.Frontiers in immunology · 2025Review
- In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection.The Journal of infectious diseases · 2024Article
- Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Lung Epithelium Releases Growth Differentiation Factor 15 in Response to Pathogen-mediated Injury.American journal of respiratory cell and molecular biology · 2024Article
- Article
- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- Effect ofFrontiers in microbiology · 2024Article
- Investigation of a UPR-Related Gene Signature Identifies the Pro-Fibrotic Effects of Thrombospondin-1 by Activating CD47/ROS/Endoplasmic Reticulum Stress Pathway in Lung Fibroblasts.Antioxidants (Basel, Switzerland) · 2023Article
- Why do humans need thrombospondin-1?Journal of cell communication and signaling · 2023Review
- TMPRSS11E-dward Scissorhands? Proteolysis Potentiates Lung Inflammation during Pathogen Insult.American journal of respiratory cell and molecular biology · 2023Article
- Chemical Optimization of SelectiveACS infectious diseases · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Acute lung injury is characterized by excessive extracellular matrix proteolysis and neutrophilic inflammation. A major risk factor for lung injury is bacterial pneumonia. However, host factors that protect against pathogen-induced and host-sustained proteolytic injury following infection are poorly understood. Pseudomonas aeruginosa (PA) is a major cause of nosocomial pneumonia and secretes proteases to amplify tissue injury. We show that thrombospondin-1 (TSP-1), a matricellular glycoprotein released during inflammation, dose-dependently inhibits PA metalloendoprotease LasB, a virulence factor. TSP-1-deficient (Thbs1-/-) mice show reduced survival, impaired host defense, and increased lung permeability with exaggerated neutrophil activation following acute intrapulmonary PA infection. Administration of TSP-1 from platelets corrects the impaired host defense and aberrant injury in Thbs1-/- mice. Although TSP-1 is cleaved into 2 fragments by PA, TSP-1 substantially inhibits Pseudomonas elastolytic activity. Administration of LasB inhibitor, genetic disabling of the PA type II secretion system, or functional deletion of LasB improves host defense and neutrophilic inflammation in mice. Moreover, TSP-1 provides an additional line of defense by directly subduing host-derived proteolysis, with dose-dependent inhibition of neutrophil elastase from airway neutrophils of mechanically ventilated critically ill patients. Thus, a host matricellular protein provides dual levels of protection against pathogen-initiated and host-sustained proteolytic injury following microbial trigger.
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.