Evidence map›Paper›PMID 29284606›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Growth Differentiation Factor 6 Promotes Vascular Stability by Restraining Vascular Endothelial Growth Factor Signaling.

Shlomo Krispin, Amber N Stratman, Chase H Melick, Radu V Stan, Matteo Malinverno, Jamie Gleklen, Daniel Castranova, Elisabetta Dejana, Brant M Weinstein

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

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  14. Outside-in Signaling by Adventitial Fibroblasts.Arteriosclerosis, thrombosis, and vascular biology · 2021
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  17. Annual Report on Sex in Preclinical Studies:Arteriosclerosis, thrombosis, and vascular biology · 2020
    Review
  18. Vascular Development.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Review
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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

9 authors at 2 institutions in 2 countries.

Shlomo KrispinFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Amber N StratmanFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Chase H MelickFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Radu V StanFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Matteo MalinvernoFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Jamie GleklenFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Daniel CastranovaFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Elisabetta DejanaFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.).
Brant M WeinsteinFrom the Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD (S.K., A.N.S., C.H.M., J.G., D.C., B.M.W.); Departments of Biochemistry and Cell Biology and of Pathology, Geisel School of Medicine at Dartmouth College, Lebanon, NH (R.V.S.); Vascular Biology Program, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan, Italy (M.M., E.D.); and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden (E.D.). flyingfish2@nih.gov.
Dartmouth College · USFIRC Institute of Molecular Oncology · IT

Funding

Regulation of Vascular IntegrityZIAHD008915 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI WEINSTEIN, BRANT · 2011 to 2025
$9.2M
Mechanism of fenestrae assembly in mammalian endothelial cellsR01GM120592 · NIGMS · DARTMOUTH COLLEGE · PI STAN, RADU VIRGIL · 2016 to 2019
$1.3M
Anti-PV1 Therapy for Pancreatic CancerR21CA172983 · NCI · DARTMOUTH COLLEGE · PI CARRIERE, CATHERINE, STAN, RADU VIRGIL · 2013 to 2014
$382k
Plasmalemma vesicle-associated protein (PV-1) as a novel target in cancer immunotR21CA175592 · NCI · DARTMOUTH COLLEGE · PI STAN, RADU VIRGIL · 2013 to 2014
$382k
Intramural NIH HHS ZIA HD008915NCI NIH HHS R21 CA172983NCI NIH HHS R21 CA175592NHLBI NIH HHS K99 HL125683NIGMS NIH HHS R01 GM120592
6 · The paper itself

Abstract

objectiveThe assembly of a functional vascular system requires a coordinated and dynamic transition from activation to maturation. High vascular endothelial growth factor activity promotes activation, including junction destabilization and cell motility. Maturation involves junctional stabilization and formation of a functional endothelial barrier. The identity and mechanism of action of prostabilization signals are still mostly unknown. Bone morphogenetic protein receptors and their ligands have important functions during embryonic vessel assembly and maturation. Previous work has suggested a role for growth differentiation factor 6 (GDF6; bone morphogenetic protein 13) in vascular integrity although GDF6's mechanism of action was not clear. Therefore, we sought to further explore the requirement for GDF6 in vascular stabilization. APPROACH AND

resultsWe investigated the role of GDF6 in promoting endothelial vascular integrity in vivo in zebrafish and in cultured human umbilical vein endothelial cells in vitro. We report that GDF6 promotes vascular integrity by counteracting vascular endothelial growth factor activity. GDF6-deficient endothelium has increased vascular endothelial growth factor signaling, increased vascular endothelial-cadherin Y658 phosphorylation, vascular endothelial-cadherin delocalization from cell-cell interfaces, and weakened endothelial cell adherence junctions that become prone to vascular leak.

conclusionsOur results suggest that GDF6 promotes vascular stabilization by restraining vascular endothelial growth factor signaling. Understanding how GDF6 affects vascular integrity may help to provide insights into hemorrhage and associated vascular pathologies in humans.

Indexed as

Capillary PermeabilityAnimalsAnimals, Genetically ModifiedAntigens, CDCadherin 5CadherinsCells, CulturedEmbryo, NonmammalianEndothelial CellsGene Expression Regulation, DevelopmentalGrowth Differentiation Factor 6HumansHuman Umbilical Vein Endothelial CellsMitogen-Activated Protein Kinase 3Neovascularization, PhysiologicPhosphorylationAntigens, CDCadherin 5Cadherinsgdf6a protein, zebrafishGDF6 protein, humanGrowth Differentiation Factor 6KDR protein, humanMitogen-Activated Protein Kinase 3Vascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Vegfaa protein, zebrafishVEGFA protein, humanZebrafish Proteinsbone morphogenetic protein receptorscadherinsgrowth differentiation factor 6human umbilical vein endothelial cellsvascular endothelial growth factor A

Identifiers

PMID29284606
PMCPMC5785447
OpenAlexW2777521817

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Registered trials

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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.