ArticleThe Journal of clinical investigation2019
RASA1-dependent cellular export of collagen IV controls blood and lymphatic vascular development.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 65 citations in OpenAlex.
- From Somatic Driver to Molecular Therapy in Retinal, Choroidal and Periocular Vascular Disease: Mosaicism, Targetable Pathways and Ocular Toxicity.International journal of molecular sciences · 2026Review
- SYVN1-provoked RASA1 ubiquitination promotes pulmonary inflammation in chronic obstructive pulmonary disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Cardiac lymphatics: functional plasticity in development, disease, and precision-targeted therapies.Basic research in cardiology · 2026Review
- Reconstruction of the lymphatic system by transplantation of a centrifuge-based bioengineered lymphatic tissue.Nature communications · 2025Article
- Reversal of cerebrovascular anomalies in a zebrafish model of vein of Galen aneurysm.Nature cardiovascular research · 2025Article
- 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
- Ras p21 protein activator 1 regulates trophoblast function and its association with preeclampsia through the Ras/mitogen-activated protein kinase pathway.CytoJournal · 2025Article
- Extracellular vesicles derived from creeping fat stem cells promote lymphatic function and restrain inflammation of Crohn's disease.Clinical and translational medicine · 2024Article
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.JCI insight · 2024Article
- A proteomics approach to isolating neuropilin-dependent α5 integrin trafficking pathways: neuropilin 1 and 2 co-traffic α5 integrin through endosomal p120RasGAP to promote polarised fibronectin fibrillogenesis in endothelial cells.Communications biology · 2024Article
- 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
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Article
- Extracellular matrix molecules associated with lymphatic vessels in health and disease.Histology and histopathology · 2024Review
- 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
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Combined germline and somatic second hit inactivating mutations of the RASA1 gene, which encodes a negative regulator of the Ras signaling pathway, cause blood and lymphatic vascular lesions in the human autosomal dominant vascular disorder capillary malformation-arteriovenous malformation (CM-AVM). How RASA1 mutations in endothelial cells (EC) result in vascular lesions in CM-AVM is unknown. Here, using different murine models of RASA1-deficiency, we found that RASA1 was essential for the survival of EC during developmental angiogenesis in which primitive vascular plexuses are remodeled into hierarchical vascular networks. RASA1 was required for EC survival during developmental angiogenesis because it was necessary for export of collagen IV from EC and deposition in vascular basement membranes. In the absence of RASA1, dysregulated Ras mitogen-activated protein kinase (MAPK) signal transduction in EC resulted in impaired folding of collagen IV and its retention in the endoplasmic reticulum (ER) leading to EC death. Remarkably, the chemical chaperone, 4-phenylbutyric acid, and small molecule inhibitors of MAPK and 2-oxoglutarate dependent collagen IV modifying enzymes rescued ER retention of collagen IV and EC apoptosis and resulted in normal developmental angiogenesis. These findings have important implications with regards an understanding of the molecular pathogenesis of CM-AVM and possible means of treatment.
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.