Silencing of STAT4 Protects Against Autoimmune Myocarditis by Regulating Th1/Th2 Immune Response via Inactivation of the NF-κB Pathway in Rats

Xue, Yulong; Zhang, Sheng‐Xiao; Zheng, Chunhua; Li, Yufeng; Zhang, Lihui; Hao, Yu‐Fei; Wang, Shu; Li, Xuewen

doi:10.1007/s10753-019-00978-3

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…Inhibition of HDAC3 activity following miR-193b-3p treatment reduced expression levels of these inflammatory cytokines in vivo. NF-κB should be a transcription factor of inflammatory mediators that plays a key role in neuroinflammation [46,47]. MiR-193b-3p significantly increased NF-κB p65 acetylation and reduced its transcriptional activity after SAH, suggesting that miR-193b-3p exerts neuroprotective effects.…”

Section: Discussionmentioning

confidence: 99%

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Lai

Liang

et al. 2020

J Neuroinflammation

133

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Background: Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation. Methods: Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels. Results: NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH. Conclusions: Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.

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Section: Discussionmentioning

confidence: 99%

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Lai

Liang

et al. 2020

J Neuroinflammation

133

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“…For example, leakage of intracellular components from damaged cardiomyocytes trigger an innate immune responses by activating TLR4. 63 Once activated, downstream signaling cascades transfer information about the extracellular pathogen into intracellular transcription factors such as NF-κB 64 and STAT3 65 to elicit a cellular response. During the recent COVID-19 pandemic, several groups have reported SARS-CoV-2 induced FM 66 and a subsequent cytokine storm.…”

Section: Pathophysiological Mechanisms Underlying Fmmentioning

confidence: 99%

Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes

Hang

Chen

Seubert

et al. 2020

Sig Transduct Target Ther

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Fulminant myocarditis (FM) is characterized by a rapid progressive decline in cardiac function and a high mortality rate. Since the first report of FM patients in the 1980s, several clinical trials and research studies have been published increasing our knowledge regarding FM. Currently, the diagnosis of FM depends on various techniques including electrocardiography, echocardiography, endomyocardial biopsy, and cardiac magnetic resonance. The development of mechanical circulation support (MCS) devices and progress in our understanding of the pathophysiological mechanisms underlying FM, treatment regimens have evolved from simple symptomatic treatment to a life support-based comprehensive treatment approach. The core mechanism underlying the development of FM is the occurrence of an inflammatory cytokine storm. This review provides a comprehensive account of the current understanding of FM pathophysiology and knowledge regarding its etiology, pathophysiology, treatments, and outcomes.

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“…On the other hand, when an antigen interacts with the variable region of the T cell receptor, acquired immunity will be activated (10). Data have shown that myocarditis is closely related to signaling pathways, such as NF-κB (11), AKT/caspase-3 (12), IL-1β (13), MAPK (14), and TLR-4/NF-κB p65 (15). However, little attention has been focused on the molecular mechanism of the immune system of AFM patients.…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA Expression Profile and Functional Analysis in Children With Acute Fulminant Myocarditis

et al. 2019

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Long non-coding RNA (lncRNA) has been associated with human diseases. To study the role of lncRNA in the pathogenic mechanism of acute fulminant myocarditis (AFM), we used a microarray to analyze lncRNA and messenger RNA (mRNA) expression in leukocyte samples from AFM patients and normal children. In total, using a 2/0.5-fold change and P < 0.05 as the cutoff criteria, we found that 3,101 lncRNAs and 2,170 mRNAs were differentially expressed in AFM patients. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis was used to verify the microarray data. Eight differentially expressed molecules were randomly selected, including 3 upregulated lncRNAs, 3 downregulated lncRNAs, and 2 upregulated mRNAs. Among them, 7 expression profiles were consistent with the microarray results. Gene Ontology enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were used to investigate the biological functions of these genes. Establishment of a lncRNA-mRNA co-expression network and lncRNA target predication were performed to study the molecular interactions of these molecules. Our study is the first to use microarrays to examine the lncRNA and mRNA expression profiles associated with AFM, and the results indicate that the immune system plays an important role in AFM. These findings may provide a new perspective for the pathogenesis, diagnosis, and therapy of AFM.

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Silencing of STAT4 Protects Against Autoimmune Myocarditis by Regulating Th1/Th2 Immune Response via Inactivation of the NF-κB Pathway in Rats

Cited by 15 publications

References 23 publications

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

Fulminant myocarditis: a comprehensive review from etiology to treatments and outcomes

Long Non-coding RNA Expression Profile and Functional Analysis in Children With Acute Fulminant Myocarditis

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