Evidence map›Paper›PMID 37609838›Full record

ArticleCirculation2023

Abnormal Lymphatic Sphingosine-1-Phosphate Signaling Aggravates Lymphatic Dysfunction and Tissue Inflammation.

Dongeon Kim, Wen Tian, Timothy Ting-Hsuan Wu, Menglan Xiang, Ryan Vinh, Jason Lon Chang, Shenbiao Gu, Seunghee Lee, Yu Zhu, Torrey Guan and 8 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Lung Lymphatics in Edema, Inflammation, and Thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2025
    Review
  10. Article
  11. Review
  12. Leukocyte-lymphatic intersections during cardiac inflammation.Journal of molecular and cellular cardiology · 2025
    Review
  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 2 countries.

Dongeon Kim *VA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Wen Tian *VA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Timothy Ting-Hsuan WuStanford University School of Medicine, CA (D.K., W.T., T.T.-H.W., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., P.K., J.P., S.G.R., X.J., M.R.N.).ORCID 0000-0002-6869-362X
Menglan XiangVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0003-4234-4998
Ryan VinhVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0002-5379-7469
Jason Lon ChangVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0002-8635-1156
Shenbiao GuVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Seunghee LeeVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0001-9156-4298
Yu ZhuVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0002-3250-6546
Torrey GuanVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Emilie Claire SchneiderVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Evan BaoVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
J Brandon DixonGeorgia Institute of Technology, Atlanta (J.B.D.).
Peter KaoStanford University School of Medicine, CA (D.K., W.T., T.T.-H.W., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., P.K., J.P., S.G.R., X.J., M.R.N.).ORCID 0000-0003-2968-5456
Junliang PanVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).
Stanley G RocksonStanford University School of Medicine, CA (D.K., W.T., T.T.-H.W., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., P.K., J.P., S.G.R., X.J., M.R.N.).ORCID 0000-0003-1253-474X
Xinguo JiangVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0003-3266-9238
Mark Robert NicollsVA Palo Alto Health Care System, Palo Alto, CA (D.K., W.T., M.X., R.V., J.L.C., S.G., S.L., Y.Z., T.G., E.C.S., E.B., J.P., X.J., M.R.N.).ORCID 0000-0001-9473-7422
VA Palo Alto Health Care System · USNorwegian Womens Public Health Association · NOGeorgia Institute of Technology · USStanford Medicine · US

Funding

T32 Training Program in Mechanisms and Innovation in Vascular DiseaseT32HL098049 · NHLBI · STANFORD UNIVERSITY · PI Nicholas James Leeper, Philip S Tsao · 2010 to 2026
$6.3M
Critical Role for Microvasculature in Airway TransplantationR01HL095686 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI NICOLLS, MARK ROBERT · 2010 to 2022
$4.7M
A Critical Role for Leukotriene B4 in LymphedemaR01HL141105 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI NICOLLS, MARK ROBERT · 2019 to 2022
$2.3M
A Critical Role for Hypoxia-Inducible Factors in LymphedemaR01HL150583 · NHLBI · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI JIANG, XINGUO · 2021 to 2024
$2.3M
NHLBI NIH HHS R01 HL095686NHLBI NIH HHS R01 HL141105NHLBI NIH HHS R01 HL150583NHLBI NIH HHS T32 HL098049
6 · The paper itself

Abstract

backgroundLymphedema is a global health problem with no effective drug treatment. Enhanced T-cell immunity and abnormal lymphatic endothelial cell (LEC) signaling are promising therapeutic targets for this condition. Sphingosine-1-phosphate (S1P) mediates a key signaling pathway required for normal LEC function, and altered S1P signaling in LECs could lead to lymphatic disease and pathogenic T-cell activation. Characterizing this biology is relevant for developing much needed therapies.

methodsHuman and mouse lymphedema was studied. Lymphedema was induced in mice by surgically ligating the tail lymphatics. Lymphedematous dermal tissue was assessed for S1P signaling. To verify the role of altered S1P signaling effects in lymphatic cells, LEC-specific

resultsHuman and experimental lymphedema tissues exhibited decreased LEC S1P signaling through S1P receptor 1 (S1PR1). LEC

conclusionsThis study suggests that reduction of the LEC S1P signaling aggravates lymphedema by enhancing LEC adhesion and amplifying pathogenic CD4 T-cell responses. P-selectin inhibitors are suggested as a possible treatment for this pervasive condition.

Indexed as

LymphedemaP-SelectinAnimalsHumansInflammationLysophospholipidsMiceSignal TransductionSphingosineLysophospholipidsP-SelectinSphingosinesphingosine 1-phosphatelymphatic endothelial cellslymphedemaP-selectinsphingosine-1-phosphate receptors 1T lymphocytes

Identifiers

PMID37609838
PMCPMC10592179
OpenAlexW4386084264

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.