ArticleThe Journal of experimental medicine2011
Severe lung fibrosis requires an invasive fibroblast phenotype regulated by hyaluronan and CD44.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 252 papers.
What it found
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Who cites it
252 citing papers in PubMed, 391 citations in OpenAlex.
- Nedd4L-mediated stabilization of morphogenetic protein receptor 2 in lung fibroblasts confers protection against pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Single-cell multiomic analysis of mesenchymal cells reveals molecular signatures and regulators of lung allograft fibrosis.JCI insight · 2026Article
- Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis.JCI insight · 2026Article
- Glycosaminoglycans in tissue regeneration: Insights into glycobiology and their biomedical application.Bioactive materials · 2026Review
- Spatially Distinct Macrophage Subsets Drive Myofibroblast Heterogeneity and Maladaptive Fibrosis in Lupus Nephritis.bioRxiv : the preprint server for biology · 2026Article
- Integration of bioinformatics analysis and experimental verification reveals the role of neutrophil extracellular traps in silica nanoparticles-induced lung injury.Journal of nanobiotechnology · 2026Article
- A single-cell and spatial transcriptomic atlas of human tuberculous constrictive pericardium.EBioMedicine · 2026Article
- Lymphatic disruption drives lung transplant fibrosis through interleukin-1-mediated hyaluronan accumulation.Science translational medicine · 2026Article
- Aberrant cellular communities underlying disease heterogeneity in chronic obstructive pulmonary disease.Nature genetics · 2026Article
- Mechanobiology and Resolution of Lung Fibrosis.Annual review of physiology · 2026Review
- Versican expression from lung fibroblasts suppresses pulmonary fibrosis.Nature communications · 2026Article
- Article
- Antimicrobial Activity Versus Virulence Potential of Hyaluronic Acid: Balancing Advantages and Disadvantages.International journal of molecular sciences · 2025Review
- Aberrant intermediate alveolar epithelial cells promote pathogenic activation of lung fibroblasts in preclinical fibrosis models.Nature communications · 2025Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Lung tissue viscoelasticity is preserved with bleomycin-induced fibrosis in mice.bioRxiv : the preprint server for biology · 2025Article
- Dissecting crosstalk induced by cell-cell communication using single-cell transcriptomic data.Nature communications · 2025Article
- Mechanisms on How Matricellular Microenvironments Sustain Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts.Acta pharmaceutica Sinica. B · 2025Article
- Shared roles of immune and stromal cells in the pathogenesis of human bronchiolitis obliterans syndrome.JCI insight · 2025Article
192 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Tissue fibrosis is a major cause of morbidity, and idiopathic pulmonary fibrosis (IPF) is a terminal illness characterized by unremitting matrix deposition in the lung. The mechanisms that control progressive fibrosis are unknown. Myofibroblasts accumulate at sites of tissue remodeling and produce extracellular matrix components such as collagen and hyaluronan (HA) that ultimately compromise organ function. We found that targeted overexpression of HAS2 (HA synthase 2) by myofibroblasts produced an aggressive phenotype leading to severe lung fibrosis and death after bleomycin-induced injury. Fibroblasts isolated from transgenic mice overexpressing HAS2 showed a greater capacity to invade matrix. Conditional deletion of HAS2 in mesenchymal cells abrogated the invasive fibroblast phenotype, impeded myofibroblast accumulation, and inhibited the development of lung fibrosis. Both the invasive phenotype and the progressive fibrosis were inhibited in the absence of CD44. Treatment with a blocking antibody to CD44 reduced lung fibrosis in mice in vivo. Finally, fibroblasts isolated from patients with IPF exhibited an invasive phenotype that was also dependent on HAS2 and CD44. Understanding the mechanisms leading to an invasive fibroblast phenotype could lead to novel approaches to the treatment of disorders characterized by severe tissue fibrosis.
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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.