Transcriptomic profiling of platelet senescence and platelet extracellular vesicles

Pienimaeki‐Roemer, Annika; Konovalova, Tatiana; Musri, Melina M.; Sigrüener, Alexander; Boettcher, Alfred; Meister, Gunter; Schmitz, Gerd

doi:10.1111/trf.13896

Cited by 39 publications

(33 citation statements)

References 111 publications

(151 reference statements)

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“…However, there are a few biological mechanisms that can endorse our finding. miR‐144‐3p has enriched expression and in the brain, as well as in normal and malignant hematopoietic cells and tissues . Many studies have suggested that miR‐144‐3p was involved in the response to stress, ageing diseases and mood stabilizer treatment .…”

Section: Discussionmentioning

confidence: 99%

“…miR-144-3p has enriched expression and in the brain, as well as in normal and malignant hematopoietic cells and tissues. 44 Many studies have suggested that miR-144-3p was involved in the response to stress, ageing diseases and mood stabilizer treatment. 19,45,46 In addition, miR-144-3p can regulate ataxin 1 (ATXN1) mRNA expression in human cells, and a search of the Genetic Association Database shows that ATXN1 is associated F I G U R E 6 Correlation between miRNAs and their target mRNAs expression in the NAc tissue.…”

Section: Discussionmentioning

confidence: 99%

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The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression‐like behaviours in mice

Zhang

Wang

et al. 2019

J Cellular Molecular Medi

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Depression is the most frequent psychiatric disorder in the world. Recent evidence has shown that stress‐induced GABAergic dysfunction in the nucleus accumbens (NAc) contributed to the pathophysiology of depression. However, the molecular mechanisms underlying these pathological changes remain unclear. In this study, mice were constantly treated with the chronic unpredictable mild stress (CUMS) till showing depression‐like behaviours expression. GABA synthesis, release and uptake in the NAc tissue were assessed by analysing the expression level of genes and proteins of Gad‐1, VGAT and GAT‐3 by qRT‐PCR and Western blotting. The miRNA/mRNA network regulating GABA was constructed based on the bioinformatics prediction software and further validated by dual‐luciferase reporter assay in vitro and qRT‐PCR in vivo, respectively. Our results showed that the expression level of GAT‐3, Gad‐1 and VGAT mRNA and protein significantly decreased in the NAc tissue from CUMS‐induced depression‐like mice than that of control mice. However, miRNA‐144‐3p, miRNA‐879‐5p, miR‐15b‐5p and miRNA‐582‐5p that directly down‐regulated the expression of Gad‐1, VGAT and GAT‐3 were increased. In the mRNA/miRNA regulatory GABA network, Gad‐1 and VGAT were directly regulated by binding seed sequence of miR‐144‐3p, and miR‐15b‐5p, miR‐879‐5p could be served negative post‐regulators by binding to the different sites of VGAT 3′‐UTR. Chronic stress causes the impaired GABA synthesis, release and uptake by up‐regulating miRNAs and down‐regulating mRNAs and proteins, which may reveal the molecular mechanisms for the decreased GABA concentrations in the NAc tissue of CUMS‐induced depression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression‐like behaviours in mice

Zhang

Wang

et al. 2019

J Cellular Molecular Medi

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“…miR-144-3p has extensive expression nature which is enriched in human brain, additionally, also enriched in malignant hematopoietic and normal cells and tissues. 69 miR-144-3p is very conserved and has various envisaged targets in both mice and humans. Numerous investigations have revealed that miR-144-3p was implicated against response to stress, aging diseases, and mood stabilizer treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Identification of key genes, pathways and miRNA/mRNA regulatory networks of CUMS-induced depression in nucleus accumbens by integrated bioinformatics analysis</p>

Zhang

Wei

et al. 2019

NDT

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Introduction: Major depressive disorder (MDD) is a recurrent, devastating mental disorder, which affects .350 million people worldwide, and exerts substantial public health and financial costs to society. Thus, there is a significant need to discover innovative therapeutics to treat depression efficiently. Stress-induced dysfunction in the subtype of neuronal cells and the change of synaptic plasticity and structural plasticity of nucleus accumbens (NAc) are implicated in depression symptomology. However, the molecular and epigenetic mechanisms and stresses to the NAc pathological changes in depression remain elusive. Materials and methods: In this study, treatment group mice were treated continually with the chronic unpredictable mild stress (CUMS) until expression of depression-like behaviors were found. Depression was confirmed with sucrose preference, novelty-suppressed feeding, forced swimming, and tail suspension tests. We applied high-throughput RNA sequencing to assess microRNA expression and transcriptional profiles in the NAc tissue from depression-like behaviors mice and control mice. The regulatory network of miRNAs/mRNAs was constructed based on the high-throughput RNA sequence and bioinformatics software predictions. Results: A total of 17 miRNAs and 10 mRNAs were significantly upregulated in the NAc of CUMS-induced mice with depression-like behaviors, and 12 miRNAs and 29 mRNAs were downregulated. A series of bioinformatics analyses showed that these altered miRNAs predicted target mRNA and differentially expressed mRNAs were significantly enriched in the MAPK signaling pathway, GABAergic synapse, dopaminergic synapse, cytokine-cytokine receptor interaction, axon guidance, regulation of autophagy, and so on. Furthermore, dual luciferase report assay and qRT-PCR results validated the miRNA/mRNA regulatory network. Conclusion: The deteriorations of GABAergic synapses, dopaminergic synapses, neurotransmitter synthesis, as well as autophagy-associated apoptotic pathway are associated with the molecular pathological mechanism of CUMS-induced depression.

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“…It is a key regulator in macrophage apoptosis, cardiac hypertrophy, atherosclerosis, and heart failure [18][19][20]. Platelet extracellular vesicles exhibit upregulated miR-142-5p, which is involved in vascular and metabolic disease [21]. miR-142 is suppressed in a hypertrophic heart model and human cardiomyopathic hearts [22].…”

Section: Discussionmentioning

confidence: 99%

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Tang

Lei

et al. 2018

Acta Pharmacol Sin

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MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.

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Transcriptomic profiling of platelet senescence and platelet extracellular vesicles

Cited by 39 publications

References 111 publications

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression‐like behaviours in mice

The molecular mechanism underlying GABAergic dysfunction in nucleus accumbens of depression‐like behaviours in mice

<p>Identification of key genes, pathways and miRNA/mRNA regulatory networks of CUMS-induced depression in nucleus accumbens by integrated bioinformatics analysis</p>

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

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