Evidence map›Paper›PMID 27345948›Full record

ArticleThrombosis and haemostasis2016

Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.

Siying Zou, Alexandra M Teixeira, Mingzhu Yin, Yaozu Xiang, Juliana Xavier-Ferrucio, Ping-Xia Zhang, John Hwa, Wang Min, Diane S Krause

Open access · greenAbstract read
In one paragraph

Article in Thrombosis and haemostasis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 23% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. MicroRNA-214-3p Regulates Hypoxia-Mediated Pulmonary Artery Smooth Muscle Cell Proliferation and Migration by Targeting ARHGEF12.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  6. Arhgef1 Plays a Vital Role in Platelet Function and Thrombogenesis.Journal of the American Heart Association · 2019
    Article
  7. Potentiation of receptor responses induced by prolonged binding of GαFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  8. 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

9 authors at 1 institution in 1 country.

Siying Zou
Alexandra M Teixeira
Mingzhu Yin
Yaozu Xiang
Juliana Xavier-Ferrucio
Ping-Xia Zhang
John Hwa
Wang Min
Diane S KrauseDiane S. Krause, Yale Stem Cell Center, 10 Amistad Street, Room 214I, New Haven, CT 06509, USA, Tel.: +1 203 785 7089, Fax: +1 203 785 4305, E-mail: diane.krause@yale.edu.
Yale University · US

Funding

Yale Cooperative Hematology Specialized Core CenterU54DK106857 · NIDDK · YALE UNIVERSITY · PI JOHN HWA, Diane S Krause · 2015 to 2026
$9.7M
Yale Center of Excellence in Molecular HematologyP30DK072442 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2005 to 2010
$5.2M
Hyperglycemia, thromboxane and platelet activity in diabetes mellitusR01HL115247 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2012 to 2019
$3.8M
Platelet Mitochondrial Function in Health and DiseaseR01HL122815 · NHLBI · YALE UNIVERSITY · PI HWA, JOHN · 2015 to 2023
$3.7M
Mechanisms of megakaryocyte maturationR01DK094934 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2012 to 2016
$2.7M
MKL in megakaryocytopoiesisR01DK086267 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2010 to 2013
$1.5M
NHLBI NIH HHS R01 HL115247NHLBI NIH HHS R01 HL122815NIDDK NIH HHS P30 DK072442NIDDK NIH HHS R01 DK086267NIDDK NIH HHS R01 DK094934NIDDK NIH HHS U54 DK106857
6 · The paper itself

Abstract

Leukemia-Associated RhoGEF (LARG) is highly expressed in platelets, which are essential for maintaining normal haemostasis. We studied the function of LARG in murine and human megakaryocytes and platelets with Larg knockout (KO), shRNA-mediated knockdown and small molecule-mediated inhibition. We found that LARG is important for human, but not murine, megakaryocyte maturation. Larg KO mice exhibit macrothrombocytopenia, internal bleeding in the ovaries and prolonged bleeding times. KO platelets have impaired aggregation, α-granule release and integrin α2bβ3 activation in response to thrombin and thromboxane, but not to ADP. The same agonist-specific reductions in platelet aggregation occur in human platelets treated with a LARG inhibitor. Larg KO platelets have reduced RhoA activation and myosin light chain phosphorylation, suggesting that Larg plays an agonist-specific role in platelet signal transduction. Using two different in vivo assays, Larg KO mice are protected from in vivo thrombus formation. Together, these results establish that LARG regulates human megakaryocyte maturation, and is critical for platelet function in both humans and mice.

Indexed as

AnimalsBleeding TimeBlood PlateletsGene Knockdown TechniquesHumansMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutMyosin Light ChainsPlatelet Function TestsrhoA GTP-Binding Proteinrho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsThrombinThrombopoiesisARHGEF12 protein, humanArhgef12 protein, mouseMyosin Light ChainsrhoA GTP-Binding ProteinRHOA protein, humanRhoA protein, mouserho GTP-Binding ProteinsRho Guanine Nucleotide Exchange FactorsThrombinThromboxanes

Identifiers

PMID27345948
PMCPMC5845781
OpenAlexW2471783055

What OpenQuestion holds

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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.