ArticleThe Journal of clinical investigation2012
RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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The trial behind it
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Who cites it
77 citing papers in PubMed, 128 citations in OpenAlex.
- An abnormal lymphatic phenotype is associated with subcutaneous adipose tissue deposits in Dercum's disease.Obesity (Silver Spring, Md.) · 2014Trial
- Lymphatic abnormalities are associated with RASA1 gene mutations in mouse and man.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- The C2 domain augments Ras GTPase-activating protein catalytic activity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- From bench to bedside: murine models of inherited and sporadic brain arteriovenous malformations.Angiogenesis · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Genomic regions, candidate genes, and pleiotropic variants associated with physiological and anatomical indicators of heat stress response in lactating sows.BMC genomics · 2024Article
- Central conducting lymphatic anomaly: from bench to bedside.The Journal of clinical investigation · 2024Review
- A temporally-restricted pattern of endothelial cell collagen 4 alpha 1 expression during embryonic development determined with a novel knockin Col4a1-P2A-eGFP mouse line.Genesis (New York, N.Y. : 2000) · 2024Article
- Review
- Response of lymphatic endothelial cells to combined spatial and temporal variations in fluid flow.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Generation and application of endogenously floxed alleles for cell-specific knockout in zebrafish.Developmental cell · 2023Article
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
- Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions.Journal of vascular anomalies · 2023Review
- EPHB4-RASA1-Mediated Negative Regulation of Ras-MAPK Signaling in the Vasculature: Implications for the Treatment of EPHB4- and RASA1-Related Vascular Anomalies in Humans.Pharmaceuticals (Basel, Switzerland) · 2023Review
- A case of malignant phyllodes tumor that responded to pazopanib and developed pneumothorax.International cancer conference journal · 2023Article
- Imaging peripheral lymphatic dysfunction in chronic conditions.Frontiers in physiology · 2023Review
17 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
7 authors at 4 institutions in 3 countries.
Funding
Abstract
RASA1 (also known as p120 RasGAP) is a Ras GTPase-activating protein that functions as a regulator of blood vessel growth in adult mice and humans. In humans, RASA1 mutations cause capillary malformation-arteriovenous malformation (CM-AVM); whether it also functions as a regulator of the lymphatic vasculature is unknown. We investigated this issue using mice in which Rasa1 could be inducibly deleted by administration of tamoxifen. Systemic loss of RASA1 resulted in a lymphatic vessel disorder characterized by extensive lymphatic vessel hyperplasia and leakage and early lethality caused by chylothorax (lymphatic fluid accumulation in the pleural cavity). Lymphatic vessel hyperplasia was a consequence of increased proliferation of lymphatic endothelial cells (LECs) and was also observed in mice in which induced deletion of Rasa1 was restricted to LECs. RASA1-deficient LECs showed evidence of constitutive activation of Ras in situ. Furthermore, in isolated RASA1-deficient LECs, activation of the Ras signaling pathway was prolonged and cellular proliferation was enhanced after ligand binding to different growth factor receptors, including VEGFR-3. Blockade of VEGFR-3 was sufficient to inhibit the development of lymphatic vessel hyperplasia after loss of RASA1 in vivo. These findings reveal a role for RASA1 as a physiological negative regulator of LEC growth that maintains the lymphatic vasculature in a quiescent functional state through its ability to inhibit Ras signal transduction initiated through LEC-expressed growth factor receptors such as VEGFR-3.
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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.