ArticleAmerican journal of physiology. Lung cellular and molecular physiology2020
Alveolar heparan sulfate shedding impedes recovery from bleomycin-induced lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Airway macrophage specific glycocalyx expression and remodeling following viral infection.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Burn-Related Glycocalyx Derangement and the Emerging Role of MMP8 in Syndecan Shedding.Biology · 2025Article
- First contact: an interdisciplinary guide into decoding H5N1 influenza virus interactions with glycosaminoglycans in 3D respiratory cell models.Frontiers in cellular and infection microbiology · 2025Review
- Cellular Mechanisms of Lung Injury: Current Perspectives.Clinics in chest medicine · 2024Review
- Glycosaminoglycan microarrays for studying glycosaminoglycan-protein systems.Carbohydrate polymers · 2024Review
- Multivalent, calcium-independent binding of surfactant protein A and D to sulfated glycosaminoglycans of the alveolar epithelial glycocalyx.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The role of human extracellular matrix proteins in defining Staphylococcus aureus biofilm infections.FEMS microbiology reviews · 2024Review
- Matrix metalloproteinases mediate influenza A-associated shedding of the alveolar epithelial glycocalyx.PloS one · 2024Article
- Article
- The unremarkable alveolar epithelial glycocalyx: a thorium dioxide-based electron microscopic comparison after heparinase or pneumolysin treatment.Histochemistry and cell biology · 2023Article
- The role of the alveolar epithelial glycocalyx in acute respiratory distress syndrome.American journal of physiology. Cell physiology · 2023Review
- Advancing Precision Medicine for the Diagnosis and Treatment of Acute Respiratory Distress Syndrome.Journal of clinical medicine · 2023Review
- Role of heparanase in ARDS through autophagy and exosome pathway (review).Frontiers in pharmacology · 2023Review
- The influenza-injured lung microenvironment promotes MRSA virulence, contributing to severe secondary bacterial pneumonia.Cell reports · 2022Article
- Fibroblast growth factor 10 attenuates chronic obstructive pulmonary disease by protecting against glycocalyx impairment and endothelial apoptosis.Respiratory research · 2022Article
- Proteoglycans in Toll-like receptor responses and innate immunity.American journal of physiology. Cell physiology · 2022Review
- Thromboprophylaxis for COVID-19-related coagulopathy: what next?European heart journal. Cardiovascular pharmacotherapy · 2022Article
- Alveolar epithelial glycocalyx degradation mediates surfactant dysfunction and contributes to acute respiratory distress syndrome.JCI insight · 2022Article
- Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment-From Mice to Men.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
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Abstract
The pulmonary epithelial glycocalyx, an anionic cell surface layer enriched in glycosaminoglycans such as heparan sulfate and chondroitin sulfate, contributes to the alveolar barrier. Direct injury to the pulmonary epithelium induces shedding of heparan sulfate into the air space; the impact of this shedding on recovery after lung injury is unknown. Using mass spectrometry, we found that heparan sulfate was shed into the air space for up to 3 wk after intratracheal bleomycin-induced lung injury and coincided with induction of matrix metalloproteinases (MMPs), including MMP2. Delayed inhibition of metalloproteinases, beginning 7 days after bleomycin using the nonspecific MMP inhibitor doxycycline, attenuated heparan sulfate shedding and improved lung function, suggesting that heparan sulfate shedding may impair lung recovery. While we also observed an increase in air space heparanase activity after bleomycin, pharmacological and transgenic inhibition of heparanase in vivo failed to attenuate heparan sulfate shedding or protect against bleomycin-induced lung injury. However, experimental augmentation of airway heparanase activity significantly worsened post-bleomycin outcomes, confirming the importance of epithelial glycocalyx integrity to lung recovery. We hypothesized that MMP-associated heparan sulfate shedding contributed to delayed lung recovery, in part, by the release of large, highly sulfated fragments that sequestered lung-reparative growth factors such as hepatocyte growth factor. In vitro, heparan sulfate bound hepatocyte growth factor and attenuated growth factor signaling, suggesting that heparan sulfate shed into the air space after injury may directly impair lung repair. Accordingly, administration of exogenous heparan sulfate to mice after bleomycin injury increased the likelihood of death due to severe lung dysfunction. Together, our findings demonstrate that alveolar epithelial heparan sulfate shedding impedes lung recovery after bleomycin.
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