ArticleJCI insight2017
Rapamycin reversal of VEGF-C-driven lymphatic anomalies in the respiratory tract.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Lymphatic-Immune Microenvironment Engineering via Rapamycin-Eluting Nanofibers for Meningeal Repair and Neuroprotection in Traumatic Brain Injury Rats.Research (Washington, D.C.) · 2026Article
- Lymphatic endothelial mTORC1 instructs metabolic and developmental signaling during lymphangiogenesis.Developmental cell · 2025Article
- Similarities and differences in the clinical features and management of primary lymphedema and kaposiform hemangioendothelioma associated with lymphedema in children.Frontiers in pediatrics · 2025Article
- First case report of intestinal lymphangiectasia with refractory bleeding from the duodenum, successfully treated by intra-abdominal lymphaticovenous anastomosis with venous ligation.Clinical journal of gastroenterology · 2024Article
- Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital.World journal of clinical cases · 2024Article
- Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.Journal of vascular anomalies · 2023Review
- Riding up the escaLEC-TOR for valvular health.The Journal of cell biology · 2023Article
- Mechanosensitive mTORC1 signaling maintains lymphatic valves.The Journal of cell biology · 2023Article
- Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation.The Journal of experimental medicine · 2023Article
- The molecular mechanism of Gorham syndrome: an update.Frontiers in immunology · 2023Review
- Low Efficacy of Genetic Tests for the Diagnosis of Primary Lymphedema Prompts Novel Insights into the Underlying Molecular Pathways.International journal of molecular sciences · 2022Article
- Imaging Blood Vessels and Lymphatics in Mouse Trachea Wholemounts.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Translation suppression underlies the restrained COVID-19 mRNA vaccine response in the high-risk immunocompromised group.Frontiers in immunology · 2022Article
- The Update of Treatment for Primary Intestinal Lymphangiectasia.Pediatric gastroenterology, hepatology & nutrition · 2021Review
- Individual approach for treatment of primary intestinal lymphangiectasia in children: single-center experience and review of the literature.BMC pediatrics · 2021Review
- Recent Progress in Lymphangioma.Frontiers in pediatrics · 2021Review
- Blood and lymphatic systems are segregated by the FLCN tumor suppressor.Nature communications · 2020Article
- Lymphatic Proliferation Ameliorates Pulmonary Fibrosis after Lung Injury.The American journal of pathology · 2020Article
- Gorham-Stout disease successfully treated with sirolimus (rapamycin): a case report and review of the literature.BMC musculoskeletal disorders · 2020Review
- Tuberous sclerosis complex presenting as primary intestinal lymphangiectasia: A case report.World journal of clinical cases · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Lymphatic malformations are serious but poorly understood conditions that present therapeutic challenges. The goal of this study was to compare strategies for inducing regression of abnormal lymphatics and explore underlying mechanisms. CCSP-rtTA/tetO-VEGF-C mice, in which doxycycline regulates VEGF-C expression in the airway epithelium, were used as a model of pulmonary lymphangiectasia. After doxycycline was stopped, VEGF-C expression returned to normal, but lymphangiectasia persisted for at least 9 months. Inhibition of VEGFR-2/VEGFR-3 signaling, Notch, β-adrenergic receptors, or autophagy and antiinflammatory steroids had no noticeable effect on the amount or severity of lymphangiectasia. However, rapamycin inhibition of mTOR reduced lymphangiectasia by 76% within 7 days without affecting normal lymphatics. Efficacy of rapamycin was not increased by coadministration with the other agents. In prevention trials, rapamycin suppressed VEGF-C-driven mTOR phosphorylation and lymphatic endothelial cell sprouting and proliferation. However, in reversal trials, no lymphatic endothelial cell proliferation was present to block in established lymphangiectasia, and rapamycin did not increase caspase-dependent apoptosis. However, rapamycin potently suppressed Prox1 and VEGFR-3. These experiments revealed that lymphangiectasia is remarkably resistant to regression but is responsive to rapamycin, which rapidly reduces and normalizes the abnormal lymphatics without affecting normal lymphatics.
Indexed as
Identifiers
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.