ArticleJCI insight2020
S1PR1 regulates the quiescence of lymphatic vessels by inhibiting laminar shear stress-dependent VEGF-C signaling.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 61 citations in OpenAlex.
- IFNγ-dependent metabolic reprogramming restrains an immature, pro-metastatic lymphatic state in melanoma.Cancer cell · 2026Article
- Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.Investigative ophthalmology & visual science · 2026Review
- The Effects of Hypertension on Signaling Dynamics in Rare Renal Cell Types.bioRxiv : the preprint server for biology · 2026Article
- APOA1 binding protein promotes lymphatic cell fate and lymphangiogenesis by relieving caveolae-mediated inhibition of VEGFR3 signaling.Nature communications · 2025Article
- Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus.Journal of advanced research · 2025Review
- S1PR1 regulates lymphatic valve development and tertiary lymphoid organ formation in the ileum.The Journal of experimental medicine · 2025Article
- Understanding the Lymphatic System: Tissue-on-Chip Modeling.Annual review of biomedical engineering · 2025Review
- Regulation of VEGFR3 signaling in lymphatic endothelial cells.Frontiers in cell and developmental biology · 2025Review
- Tumor cell-derived hyaluronan fragments induce endocytosis of S1PR1 to promote lymphangiogenesis through LYVE-1-Src pathway.Journal of Cancer · 2025Article
- Zonation and ligand and dose dependence of sphingosine 1-phosphate receptor-1 signalling in blood and lymphatic vasculature.Cardiovascular research · 2024Article
- EndothelialResearch square · 2024Article
- Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.American journal of physiology. Cell physiology · 2023Article
- Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation.Circulation · 2023Article
- Lymphatic vasculature in ovarian cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Abnormal lymphatic S1P signaling aggravates lymphatic dysfunction and tissue inflammation.medRxiv : the preprint server for health sciences · 2023Article
- Lessons of Vascular Specialization From Secondary Lymphoid Organ Lymphatic Endothelial Cells.Circulation research · 2023Review
- Isolation and short-term culturing of primary lymphatic endothelial cells from collecting lymphatics: A techniques study.Microcirculation (New York, N.Y. : 1994) · 2023Article
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Hydrogen sulfide donor activates AKT-eNOS signaling and promotes lymphatic vessel formation.PloS one · 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
15 authors at 6 institutions in 2 countries.
Funding
Abstract
During the growth of lymphatic vessels (lymphangiogenesis), lymphatic endothelial cells (LECs) at the growing front sprout by forming filopodia. Those tip cells are not exposed to circulating lymph, as they are not lumenized. In contrast, LECs that trail the growing front are exposed to shear stress, become quiescent, and remodel into stable vessels. The mechanisms that coordinate the opposed activities of lymphatic sprouting and maturation remain poorly understood. Here, we show that the canonical tip cell marker Delta-like 4 (DLL4) promotes sprouting lymphangiogenesis by enhancing VEGF-C/VEGF receptor 3 (VEGFR3) signaling. However, in lumenized lymphatic vessels, laminar shear stress (LSS) inhibits the expression of DLL4, as well as additional tip cell markers. Paradoxically, LSS also upregulates VEGF-C/VEGFR3 signaling in LECs, but sphingosine 1-phosphate receptor 1 (S1PR1) activity antagonizes LSS-mediated VEGF-C signaling to promote lymphatic vascular quiescence. Correspondingly, S1pr1 loss in LECs induced lymphatic vascular hypersprouting and hyperbranching, which could be rescued by reducing Vegfr3 gene dosage in vivo. In addition, S1PR1 regulates lymphatic vessel maturation by inhibiting RhoA activity to promote membrane localization of the tight junction molecule claudin-5. Our findings suggest a potentially new paradigm in which LSS induces quiescence and promotes the survival of LECs by downregulating DLL4 and enhancing VEGF-C signaling, respectively. S1PR1 dampens LSS/VEGF-C signaling, thereby preventing sprouting from quiescent lymphatic vessels. These results also highlight the distinct roles that S1PR1 and DLL4 play in LECs when compared with their known roles in the blood vasculature.
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.