ArticleScience advances
The matrikine N-α-PGP couples extracellular matrix fragmentation to endothelial permeability.
Article in Science advances. 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 trial behind it
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Who cites it
35 citing papers in PubMed, 64 citations in OpenAlex.
- Review
- Trimethylamine N-oxide (TMAO) disrupts endothelial junction integrity through VE-cadherin Tyr658 phosphorylation in vitro.Archives of toxicology · 2026Article
- Extracellular Matrix-Derived Matrikines: Circulating Peptides as Candidate Mediators of Lung-to-Brain Signaling.International journal of molecular sciences · 2026Review
- Targeting the proline-glycine-proline-protease feed-forward loop attenuates primary graft dysfunction after lung transplantation.Frontiers in immunology · 2026Article
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations.International journal of molecular sciences · 2025Article
- NMN Supplementation Inhibits Endothelial Cell ROS-Mediated Src/Pi3k/Akt Signaling Pathway to Protect High-Altitude Blood-Retinal Barrier.Investigative ophthalmology & visual science · 2025Article
- Integrin signalling in joint development, homeostasis and osteoarthritis.Nature reviews. Rheumatology · 2024Review
- Beyond the barrier: the immune-inspired pathways of tumor extravasation.Cell communication and signaling : CCS · 2024Review
- Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.Science signaling · 2023Article
- LC-MS/MS method for proline-glycine-proline and acetylated proline-glycine-proline in human plasma.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2023Article
- The short-chain fatty acid butyrate exerts a specific effect on VE-cadherin phosphorylation and alters the integrity of aortic endothelial cells.Frontiers in cell and developmental biology · 2023Article
- Efficacy of a Probiotic and Herbal Supplement in Models of Lung Inflammation.Microorganisms · 2022Article
- Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability.Microbiology spectrum · 2022Article
- Highway toFrontiers in pharmacology · 2022Review
- Regulation of vascular permeability in cancer metastasis.Cancer science · 2021Review
- A mechanism for matrikine regulation in acute inflammatory lung injury.JCI insight · 2021Article
- A narrative review of changes in microvascular permeability after burn.Annals of translational medicine · 2021Review
- Prolyl endopeptidase contributes to early neutrophilic inflammation in acute myocardial transplant rejection.JCI insight · 2021Article
- Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.Journal of cellular physiology · 2020Review
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
The compartmentalization and transport of proteins and solutes across the endothelium is a critical biologic function altered during inflammation and disease, leading to pathology in multiple disorders. The impact of tissue damage and subsequent extracellular matrix (ECM) fragmentation in regulating this process is unknown. We demonstrate that the collagen-derived matrikine acetylated proline-glycine-proline (N-α-PGP) serves as a critical regulator of endothelial permeability. N-α-PGP activates human endothelial cells via CXC-chemokine receptor 2 (CXCR2), triggering monolayer permeability through a discrete intracellular signaling pathway. In vivo, N-α-PGP induces local vascular leak after subcutaneous administration and pulmonary vascular permeability after systemic administration. Furthermore, neutralization of N-α-PGP attenuates lipopolysaccharide-induced lung leak. Finally, we demonstrate that plasma from patients with acute respiratory distress syndrome (ARDS) induces VE-cadherin phosphorylation in human endothelial cells, and this activation is attenuated by N-α-PGP blockade with a concomitant improvement in endothelial monolayer impedance. These results identify N-α-PGP as a novel ECM-derived matrikine regulating paracellular permeability during inflammatory disease and demonstrate the potential to target this ligand in various disorders characterized by excessive matrix turnover and vascular leak such as ARDS.
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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.