ArticleThe American journal of pathology2020
Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury.
Article in The American journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Keratin 20 deficiency phenocopies human UAB and drives bladder fibrosis via a mechanotransduction-TGF-β axis.iScience · 2026Article
- Prolongation of Postoperative Drainage Time in Indocyanine Green Lymphography as a Potential Marker for Lymphedema Development-A Prospective Pilot Study.Journal of clinical medicine · 2026Article
- Histone demethylase KDM7A negatively regulates fibrotic macrophage polarization and lung fibrosis progression.Communications biology · 2026Article
- Article
- Article
- Lung Lymphatics in Edema, Inflammation, and Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.Nature cardiovascular research · 2025Article
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.The Journal of experimental medicine · 2025Article
- Mice with lymphatic dysfunction develop pathogenic lung tertiary lymphoid organs that model an autoimmune emphysema phenotype of COPD.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Review
- Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.bioRxiv : the preprint server for biology · 2024Article
- Influenza induces lung lymphangiogenesis independent of YAP/TAZ activity in lymphatic endothelial cells.Scientific reports · 2024Article
- Endothelial cell expression of a STING gain-of-function mutation initiates pulmonary lymphocytic infiltration.Cell reports · 2024Article
- Role of Sensory Nerves in Pulmonary Fibrosis.International journal of molecular sciences · 2024Review
- Single Cell Analysis of Lung Lymphatic Endothelial Cells and Lymphatic Responses during Influenza Infection.Journal of respiratory biology and translational medicine · 2024Article
- Influenza Induces Lung Lymphangiogenesis Independent of YAP/TAZ Activity in Lymphatic Endothelial Cells.Research square · 2024Article
- EndothelialResearch square · 2024Article
- Efficient pulmonary lymphatic drainage is necessary for inflammation resolution in ARDS.JCI insight · 2024Article
- Three-dimensional visualization of the lymphatic, vascular and neural network in rat lung by confocal microscopy.Journal of molecular histology · 2023Article
- Angiogenesis-An Emerging Role in Organ Fibrosis.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Despite many reports about pulmonary blood vessels in lung fibrosis, the contribution of lymphatics to fibrosis is unknown. We examined the mechanism and consequences of lymphatic remodeling in mice with lung fibrosis after bleomycin injury or telomere dysfunction. Widespread lymphangiogenesis was observed after bleomycin treatment and in fibrotic lungs of prospero homeobox 1-enhanced green fluorescent protein (Prox1-EGFP) transgenic mice with telomere dysfunction. In loss-of-function studies, blocking antibodies revealed that lymphangiogenesis 14 days after bleomycin treatment was dependent on vascular endothelial growth factor (Vegf) receptor 3 signaling, but not on Vegf receptor 2. Vegfc gene and protein expression increased specifically. Extensive extravasated plasma, platelets, and macrophages at sites of lymphatic growth were potential sources of Vegfc. Lymphangiogenesis peaked at 14 to 28 days after bleomycin challenge, was accompanied by doubling of chemokine (C-C motif) ligand 21 in lung lymphatics and tertiary lymphoid organ formation, and then decreased as lung injury resolved by 56 days. In gain-of-function studies, expansion of the lung lymphatic network by transgenic overexpression of Vegfc in club cell secretory protein (CCSP)/VEGF-C mice reduced macrophage accumulation and fibrosis and accelerated recovery after bleomycin treatment. These findings suggest that lymphatics have an overall protective effect in lung injury and fibrosis and fit with a mechanism whereby lung lymphatic network expansion reduces lymph stasis and increases clearance of fluid and cells, including profibrotic macrophages.
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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.