ArticleAmerican journal of physiology. Lung cellular and molecular physiology2010
High-molecular-weight hyaluronan is a novel inhibitor of pulmonary vascular leakiness.
Article in American journal of physiology. Lung cellular and molecular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 88 citations in OpenAlex.
- Antimicrobial Activity Versus Virulence Potential of Hyaluronic Acid: Balancing Advantages and Disadvantages.International journal of molecular sciences · 2025Review
- Agarose Gel Electrophoresis Reveals the Molecular Weight Distribution of Hyaluronan Produced by Orbital Fibroblasts.Gels (Basel, Switzerland) · 2025Article
- Lung-Brain Axis-Generated Inflammatory Biomarkers in Traumatic Brain Injury and Acute Respiratory Distress Syndrome: Role of Mechanical Ventilation/Stress.Advances in biomarker sciences and technology · 2025Article
- Intravenous Administration of Hyaluronan in Veterinary Musculoskeletal Disorders: Therapeutic Applications and Mechanisms.International journal of veterinary science and medicine · 2025Review
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Enzymatic Modulation of the Pulmonary Glycocalyx Enhances Susceptibility toAmerican journal of respiratory cell and molecular biology · 2024Article
- Hyaluronan and Reactive Oxygen Species Signaling-Novel Cues from the Matrix?Antioxidants (Basel, Switzerland) · 2023Review
- The role of hyaluronan in endothelial glycocalyx and potential preventative lifestyle strategy with advancing age.Current topics in membranes · 2023Article
- CPAP-induced airway hyper-reactivity in mice is modulated by hyaluronan synthase-3.Pediatric research · 2022Article
- Hyaluronic acid restored protein permeability across injured human lung microvascular endothelial cells.FASEB bioAdvances · 2022Article
- Role of extracellular vesicles in severe pneumonia and sepsis.Expert opinion on biological therapy · 2022Review
- Protection and rebuilding of the endothelial glycocalyx in sepsis - Science or fiction?Matrix biology plus · 2021Article
- Therapeutic effects of high molecular weight hyaluronic acid in severeAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases.Pulmonary medicine · 2021Review
- Article
- Extracellular Superoxide Dismutase Regulates Early Vascular Hyaluronan Remodeling in Hypoxic Pulmonary Hypertension.Scientific reports · 2020Article
- Therapeutic Effects of Hyaluronic Acid in Bacterial Pneumonia inAmerican journal of respiratory and critical care medicine · 2019Article
- High Molecular Weight Hyaluronan Suppresses Macrophage M1 Polarization and Enhances IL-10 Production in PMMolecules (Basel, Switzerland) · 2019Article
- The CD44-HA axis and inflammation in atherosclerosis: A temporal perspective.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial cell (EC) barrier dysfunction results in increased vascular permeability, a perturbation observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that enhance EC barrier integrity have important therapeutic implications. We observed that binding of high-molecular-weight hyaluronan (HMW-HA) to its cognate receptor CD44 within caveolin-enriched microdomains (CEM) enhances human pulmonary EC barrier function. Immunocytochemical analysis indicated that HMW-HA promotes redistribution of a significant population of CEM to areas of cell-cell contact. Quantitative proteomic analysis of CEM isolated from human EC demonstrated HMW-HA-mediated recruitment of cytoskeletal regulatory proteins (annexin A2, protein S100-A10, and filamin A/B). Inhibition of CEM formation [caveolin-1 small interfering RNA (siRNA) and cholesterol depletion] or silencing (siRNA) of CD44, annexin A2, protein S100-A10, or filamin A/B expression abolished HMW-HA-induced actin cytoskeletal reorganization and EC barrier enhancement. To confirm our in vitro results in an in vivo model of inflammatory lung injury with vascular hyperpermeability, we observed that the protective effects of HMW-HA on LPS-induced pulmonary vascular leakiness were blocked in caveolin-1 knockout mice. Furthermore, targeted inhibition of CD44 expression in the mouse pulmonary vasculature significantly reduced HMW-HA-mediated protection from LPS-induced hyperpermeability. These data suggest that HMW-HA, via CD44-mediated CEM signaling events, represents a potentially useful therapeutic agent for syndromes of increased vascular permeability.
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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.