MicroRNA-127 Promotes Anti-microbial Host Defense through Restricting A20-Mediated De-ubiquitination of STAT3

Liu, Xiaoyi; Mao, Yun; Kang, Yanhua; He, Long; Zhu, Bo; Zhang, Wei; Lu, Yin; Wu, Qinan; Xu, Dakang; Shi, Liyun

doi:10.1016/j.isci.2019.100763

Cited by 13 publications

(9 citation statements)

References 59 publications

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“…The MRSA strain (USA300) reported by our previous study ( 16 ) was cultured in Luria Bertani broth at 37°C until its stable growth phase, and then collected by centrifugation at 8,000 rpm for 5 min. The bacteria were washed three times with PBS and resuspended to an optical density of 0.8 at 600 nm.…”

Section: Methodsmentioning

confidence: 99%

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ATF3 Positively Regulates Antibacterial Immunity by Modulating Macrophage Killing and Migration Functions

Zheng

et al. 2022

Front. Immunol.

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The clinical severity of Staphylococcus aureus (S. aureus) respiratory infection correlates with antibacterial gene signature. S. aureus infection induces the expression of an antibacterial gene, as well as a central stress response gene, thus activating transcription factor 3 (ATF3). ATF3-deficient mice have attenuated protection against lethal S. aureus pneumonia and have a higher bacterial load. We tested the hypothesis that ATF3-related protection is based on the increased function of macrophages. Primary marrow-derived macrophages (BMDM) were used in vitro to determine the mechanism through which ATF3 alters the bacterial-killing ability. The expression of ATF3 correlated with the expression of antibacterial genes. Mechanistic studies showed that ATF3 upregulated antibacterial genes, while ATF3-deficient cells and lung tissues had a reduced level of antibacterial genes, which was accompanied by changes in the antibacterial process. We identified multiple ATF3 regulatory elements in the antibacterial gene promoters by chromatin immunoprecipitation analysis. In addition, Wild type (WT) mice had higher F4/80 macrophage migration in the lungs compared to ATF3-null mice, which may correlate with actin filament severing through ATF3-targeted actin-modifying protein gelsolin (GSN) for the macrophage cellular motility. Furthermore, ATF3 positively regulated inflammatory cytokines IL-6 and IL-12p40 might be able to contribute to the infection resolution. These data demonstrate a mechanism utilized by S. aureus to induce ATF3 to regulate antibacterial genes for antimicrobial processes within the cell, and to specifically regulate the actin cytoskeleton of F4/80 macrophages for their migration.

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Section: Methodsmentioning

confidence: 99%

“…BALF collection was performed in line with our published procedure with minor modifications ( 16 ). Briefly, we sacrificed the mice by cervical dislocation and exposed the trachea.…”

Section: Methodsmentioning

confidence: 99%

ATF3 Positively Regulates Antibacterial Immunity by Modulating Macrophage Killing and Migration Functions

Zheng

et al. 2022

Front. Immunol.

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“…Antibacterial innate immunity is modulated by miR-127 via the regulation of the A20/STAT3 axis [ 55 ]. A previous study indicated that the expression levels of miR-127 were induced by Staphylococcus aureus ( S. aureus ) infection.…”

Section: Introductionmentioning

confidence: 99%

“…The anti-microbial host defense is mediated by miR-127 via targeting the A20/STAT3 axis [ 55 ]. By using miR-127 mimics and inhibitors, it was confirmed that miR-127 conferred protection against S. aureus pneumonia.…”

Section: Introductionmentioning

confidence: 99%

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

2022

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MicroRNAs (miRNAs), which were initially discovered in Caenorhabditis elegans, can regulate gene expression by recognizing cognate sequences and interfering with the transcriptional or translational machinery. The application of bioinformatics tools for structural analysis and target prediction has largely driven the investigation of certain miRNAs. Notably, it has been found that certain miRNAs which are widely involved in the inflammatory response and immune regulation are closely associated with the occurrence, development, and outcome of bacterial pneumonia. It has been shown that certain miRNA techniques can be used to identify related targets and explore associated signal transduction pathways. This enhances the understanding of bacterial pneumonia, notably for “refractory” or drug-resistant bacterial pneumonia. Although these miRNA-based methods may provide a basis for the clinical diagnosis and treatment of this disease, they still face various challenges, such as low sensitivity, poor specificity, low silencing efficiency, off-target effects, and toxic reactions. The opportunities and challenges of these methods have been completely reviewed, notably in bacterial pneumonia. With the continuous improvement of the current technology, the miRNA-based methods may surmount the aforementioned limitations, providing promising support for the clinical diagnosis and treatment of “refractory” or drug-resistant bacterial pneumonia.

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“…Studies have found that the upregulation of A20 expression can inhibit apoptosis induced by microglial exosomes ( Chen et al, 2019 ). A20 interacts with RIPK1 through its ZnF7 structural domain to affect caspase-8 protein expression in intestinal epithelial cells, thereby inhibiting their apoptosis ( Liu X. et al, 2020 ). Furthermore, A20 upregulation inhibits intestinal epithelial cell apoptosis in Crohn’s disease ( Zhou et al, 2019 ) by affecting the functions of tumor necrosis factor receptor 1 (TNFR1), TNFR1-associated death domain protein (TRADD) and RIPK1.…”

Section: Introductionmentioning

confidence: 99%

Advances in the Study of the Ubiquitin-Editing Enzyme A20

Bai

Huo

et al. 2022

Front. Pharmacol.

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Ubiquitin modification is a common post-translational protein modification and an important mechanism whereby the body regulates protein levels and functions. As a common enzyme associated with ubiquitin modification, the ubiquitin-editing enzyme A20 may be closely associated with the development of numerous pathological processes through its different structural domains. The aim of this paper is to provide an overview of the following: advances in ubiquitination research, the structure and function of A20, and the relationships between A20 and immune inflammatory response, apoptosis, necroptosis, pyroptosis, and autophagy.

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MicroRNA-127 Promotes Anti-microbial Host Defense through Restricting A20-Mediated De-ubiquitination of STAT3

Cited by 13 publications

References 59 publications

ATF3 Positively Regulates Antibacterial Immunity by Modulating Macrophage Killing and Migration Functions

ATF3 Positively Regulates Antibacterial Immunity by Modulating Macrophage Killing and Migration Functions

The current landscape of microRNAs (miRNAs) in bacterial pneumonia: opportunities and challenges

Advances in the Study of the Ubiquitin-Editing Enzyme A20

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