Evidence map›Paper›PMID 35054966›Full record

ArticleInternational journal of molecular sciences2022

PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.

Yunkyung Heo, Hyejin Jeon, Wan Namkung

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. 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
1.6field-weighted citation impact, top 16% 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, 10 citations in OpenAlex.

  1. Article
  2. Mitochondrial CaCommunications biology · 2026
    Article
  3. Article
  4. Article
  5. Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025
    Review
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  7. Review
  8. Article
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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

3 authors at 1 institution in 1 country.

Yunkyung HeoYonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea.ORCID 0000-0003-3780-7695
Hyejin JeonYonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea.ORCID 0000-0003-0711-0766
Wan NamkungYonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea.ORCID 0000-0002-1480-7433
Yonsei University · KR

Funding

Ministry of Education (MOE, Korea) through the fostering project of 'Yonsei University and Industry Cooperation Complex' supervised by the Korea Institute for Advancement of Technology (KIAT)National Research Foundation of Korea NRF-2018R1A6A1A03023718
6 · The paper itself

Abstract

Thrombin stimulates platelets via a dual receptor system of protease-activated receptors (PARs): PAR1 and PAR4. PAR1 activation induces a rapid and transient signal associated with the initiation of platelet aggregation, whereas PAR4 activation results in a prolonged signal, required for later phases, that regulates the stable formation of thrombus. In this study, we observed differential signaling pathways for thrombin-induced PAR1 and PAR4 activation in a human megakaryoblastic leukemia cell line, MEG-01. Interestingly, thrombin induced both calcium signaling and morphological changes in MEG-01 cells via the activation of PAR1 and PAR4, and these intracellular events were very similar to those observed in platelets shown in previous studies. We developed a novel image-based assay to quantitatively measure the morphological changes in living cells, and observed the underlying mechanism for PAR1- and PAR4-mediated morphological changes in MEG-01 cells. Selective inhibition of PAR1 and PAR4 by vorapaxar and BMS-986120, respectively, showed that thrombin-induced morphological changes were primarily mediated by PAR4 activation. Treatment of a set of kinase inhibitors and 2-aminoethoxydiphenyl borate (2-APB) revealed that thrombin-mediated morphological changes were primarily regulated by calcium-independent pathways and PAR4 activation-induced PI3K/Akt and RhoA/ROCK signaling pathways in MEG-01 cells. These results indicate the importance of PAR4-mediated signaling pathways in thrombin-induced morphological changes in MEG-01 cells and provide a useful in vitro cellular model for platelet research.

Indexed as

Signal TransductionBlood PlateletsCalciumCell LineFluorescent Antibody TechniqueGene ExpressionHumansMegakaryocytesModels, BiologicalPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, ThrombinrhoA GTP-Binding Proteinrho-Associated KinasesThrombinCalciumPhosphatidylinositol 3-Kinasesprotease-activated receptor 4Proto-Oncogene Proteins c-aktReceptors, ThrombinrhoA GTP-Binding ProteinRHOA protein, humanrho-Associated KinasesThrombinMEG-01morphological changePAR1PAR4plateletthrombin

Identifiers

PMID35054966
PMCPMC8775998
OpenAlexW4206611768

What OpenQuestion holds

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LicenceCC BY
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.