Evidence mapPaperPMID 32767736Full record

ArticleJournal of thrombosis and haemostasis : JTH2020

Apoptosis signal-regulating kinase 1 regulates immune-mediated thrombocytopenia, thrombosis, and systemic shock.

Pravin Patel, Noor F Shaik, Yuhang Zhou, Kalyan Golla, Steven E McKenzie, Ulhas P Naik

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. The Function of ASK1 in Sepsis and Stress-Induced Disorders.International journal of molecular sciences · 2023
    Review
  4. [Research on immunological function of platelet receptor FcγRⅡA].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2023
    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

6 authors at 1 institution in 1 country.

Pravin PatelCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.ORCID 0000-0002-7598-6121
Noor F ShaikCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Yuhang ZhouCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Kalyan GollaCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Steven E McKenzieCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Ulhas P NaikCardeza Center for Hemostasis, Thrombosis, and Vascular Biology, Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.ORCID 0000-0001-7556-444X
Thomas Jefferson University · US

Funding

Protein CoreP01HL110860 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI RAUOVA, LUBICA · 2012 to 2016
$11.4M
ASK1 a novel regulator of platelet functionR01HL113188 · NHLBI · UNIVERSITY OF DELAWARE · PI NAIK, ULHAS P · 2013 to 2022
$3.4M
NHLBI NIH HHS 2R01 HL113188-05NHLBI NIH HHS P01 HL110860NHLBI NIH HHS R01 HL113188
6 · The paper itself

Abstract

backgroundImmune complexes (ICs) bind to and activate platelets via FcγRIIA, causing patients to experience thrombocytopenia, as well as an increased risk of forming occlusive thrombi. Although platelets have been shown to mediate IC-induced pathologies, the mechanisms involved have yet to be fully elucidated. We identified that apoptosis signal-regulating kinase 1 (ASK1) is present in both human and mouse platelets and potentiates many platelet functions.

objectivesHere we set out to study ASK1's role in regulating IC-mediated platelet functions in vitro and IC-induced pathologies using an in vivo mouse model.

methodsUsing human platelets treated with an ASK1-specific inhibitor and platelets from FCGR2A/Ask1

resultsWe found that ASK1 was activated in human platelets following cross-linking of FcγRIIA using either anti-hCD9 or IV.3 + goat-anti-mouse. Although genetic deletion or inhibition of ASK1 significantly attenuated anti-CD9-induced platelet aggregation, activation of the canonical FcγRIIA signaling targets Syk and PLCγ2 was unaffected. We further found that anti-mCD9-induced cPla

conclusionsThese findings suggest that ASK1 inhibition may be a potential target for the treatment of IC-induced shock and other immune-mediated thrombotic disorders.

Indexed as

ThrombocytopeniaThrombosisAnimalsApoptosisBlood PlateletsHumansMAP Kinase Kinase Kinase 5MicePlatelet ActivationPlatelet AggregationMap3k5 protein, mouseMAP Kinase Kinase Kinase 5apoptosis signal-regulating kinase 1plateletsshockthrombocytopeniathrombosis

Identifiers

PMID32767736
PMCPMC7831975
OpenAlexW3048249037

What Socratic holds

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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 Socratic graph.