Evidence map›Paper›PMID 25336627›Full record

ArticleBlood2014

Podoplanin requires sialylated O-glycans for stable expression on lymphatic endothelial cells and for interaction with platelets.

Yanfang Pan, Tadayuki Yago, Jianxin Fu, Brett Herzog, J Michael McDaniel, Padmaja Mehta-D'Souza, Xiaofeng Cai, Changgeng Ruan, Rodger P McEver, Christopher West and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.5field-weighted citation impact, top 9% 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

35 citing papers in PubMed, 53 citations in OpenAlex.

  1. Protein O-Glycosylation Shapes Lymphatic Endothelia and Lymph Node Macrophage Populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Parallel Synthesis of Glycopeptide Libraries Using Glyco-SPOT Synthesis.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  3. Article
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  10. Science advances · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Mucin-Type O-GalNAc Glycosylation in Health and Disease.Advances in experimental medicine and biology · 2021
    Article
  15. Article
  16. Article
  17. Cosmc-dependent mucin-typeAmerican journal of physiology. Renal physiology · 2020
    Article
  18. Podoplanin in Inflammation and Cancer.International journal of molecular sciences · 2019
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Yanfang PanCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China;
Tadayuki YagoCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Jianxin FuCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Brett HerzogCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;
J Michael McDanielCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Padmaja Mehta-D'SouzaCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Xiaofeng CaiCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
Changgeng RuanJiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Rodger P McEverCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;
Christopher WestDepartment of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;
Kesheng DaiJiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Hong ChenCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK;
Lijun XiaCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK; Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Oklahoma Medical Research Foundation · USUniversity of Oklahoma Health Sciences Center · USFirst Affiliated Hospital of Soochow University · CNSoochow University · CN

Funding

Protein-glycan Interactions in the Vascular SystemP01HL085607 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CUMMINGS, RICHARD D, MCEVER, RODGER PAUL · 2006 to 2015
$16.8M
Interdisciplinary research in vascular biologyP20GM103441 · NIGMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI MCEVER, RODGER PAUL · 2012 to 2014
$7.3M
Epsin in Angiogenesis and Vascular RemodelingR01HL093242 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CHEN, HONG, WANG, DA-ZHI · 2009 to 2021
$7.3M
Mechanisms regulating VEGF receptors in diabetic angiogenesisR01HL130845 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, XU, JIAN · 2016 to 2023
$4.9M
The Role of Signaling Adaptor Protein Epsin in AtherosclerosisR01HL118676 · NHLBI · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI CHEN, HONG · 2014 to 2017
$1.8M
NHLBI NIH HHS HL085607NHLBI NIH HHS HL093242NHLBI NIH HHS HL118676NHLBI NIH HHS P01 HL085607NHLBI NIH HHS R01 HL093242NHLBI NIH HHS R01 HL118676NHLBI NIH HHS R01 HL130845NIGMS NIH HHS GM103441NIGMS NIH HHS P20 GM103441
6 · The paper itself

Abstract

O-glycosylation of podoplanin (PDPN) on lymphatic endothelial cells is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 during development. However, how O-glycosylation controls endothelial PDPN function and expression remains unclear. In this study, we report that core 1 O-glycan-deficient or desialylated PDPN was highly susceptible to proteolytic degradation by various proteases, including metalloproteinases (MMP)-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of PDPN on core 1 O-glycan-deficient endothelial cells, but not on wild-type ECs. The lymph from mice with sepsis induced by cecal ligation and puncture, which contained bacteria-derived sialidase, reduced PDPN levels on wild-type ECs. The MMP inhibitor, GM6001, rescued these reductions. Additionally, GM6001 treatment rescued the reduction of PDPN level on lymphatic endothelial cells in mice lacking endothelial core 1 O-glycan or cecal ligation and puncture-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated PDPN impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of PDPN are essential for platelet adhesion and prevent PDPN from proteolytic degradation primarily mediated by MMPs in the lymph.

Indexed as

AnimalsBlood PlateletsCell CommunicationCHO CellsCricetulusDipeptidesEndothelial CellsGene Expression RegulationGlycosylationMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMembrane GlycoproteinsMiceMice, KnockoutPlatelet AdhesivenessDipeptidesMatrix Metalloproteinase 2Matrix Metalloproteinase 9Matrix Metalloproteinase InhibitorsMembrane GlycoproteinsMmp2 protein, mouseMmp9 protein, mouseN-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamidePdpn protein, mousePodoplaninPolysaccharidesSialic Acids

Identifiers

PMID25336627
PMCPMC4256915
OpenAlexW2127953803

What OpenQuestion holds

Textmetadata
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.