MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor κB Activation and p53-Mediated Apoptotic Signaling

Ma, He; Wang, Xiaohui; Ha, Tuanzhu; Gao, Ming; Liu, Li; Wang, Ruitao; Yu, Kaijiang; Kalbfleisch, John H.; Kao, Race L.; Williams, David L.; Li, Chuanfu

doi:10.1093/infdis/jiw449

Cited by 88 publications

(59 citation statements)

References 42 publications

(117 reference statements)

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“…Previous studies have indicated TRAF6 took critical part in the processes of sepsis-induced cardiac dysfunction(Ma et al . )20, ischemia-reperfusion injury(Liu et al . )21, immunity response to virus infection(Wei et al .…”

Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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Previous studies have shown that Low intensity pulsed ultrasound(LIPUS) prevents polyethylene-debris-induced periprosthetic loosening in vivo, but the details of the mechanism by which it does so remain unclear. In this article, we used polyethylene debris induced RAW 264.7 cells as the in vitro model, and tested the effect of LIPUS on this model. Changes in the level of inflammatory cytokines, cell proliferation, and apoptosis were assessed. Gene overexpression and siRNA technique were applied, and the levels of expression of FBXL2, TRAF6, ERK, and related inflammatory cytokines were also measured. Results indicated that FBXL2-mediated TRAF6 ubiquitination and degradation also plays an important role in aseptic periprosthetic loosening process, and LIPUS prevents such loosening by strengthening this pathway.

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Section: Discussionmentioning

confidence: 99%

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao

Zhao²,

Shi

et al. 2017

Sci Rep

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“…In the mouse heart, transfection with lentivirus expressing miR-125b significantly attenuates the expression of ICAM-1 and VCAM-1, the accumulation of immune cells, and cardiac dysfunction caused by sepsis. Lentivirus expressing miR-125b also reduces serum TNF-a and IL-1b in mice, which further weakens endothelial inflammation (12).…”

Section: Mirnas Target the Receptor Complex Of Nf-kb Pathwaymentioning

confidence: 99%

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

2018

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The surface of endothelial cells is covered with cell adhesion molecules, including E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM- 1) , that mediate the adhesion and extravasation of leukocytes and play pivotal roles in inflammatory response. microRNAs (miRNAs) regulate the expression of these important cell adhesion molecules through two distinct major mechanisms, namely via modulating the proinflammatory NF-κB pathway, which controls their transcription, and via directly targeting them. The present review highlights the role of various miRNAs in controlling the expression of E-selectin, ICAM-1, and VCAM-1: a type of regulation that can be harnessed for therapeutic prevention of inflammation-associated diseases such as atherosclerosis and sepsis. The roles of secreted miRNAs as paracrine regulators, and cell adhesion molecule-based miRNA delivery are also addressed.-Zhong, L., Simard, M. J., Huot, J. Endothelial microRNAs regulating the NF-κB pathway and cell adhesion molecules during inflammation.

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“…MiR-146a could function in braking the immunity via suppressing the level of its target gene, resulting in immune cell immaturation and/or inactivation (31). In sepsis-induced cardiac dysfunction, miR-125b suppresses TNF-α and IL-1β by suppressing TRAF6, as well as markedly attenuates the myocardial apoptosis through decreasing the expression of the p53, Bax, and Bak1 (16). MCEMP1 encodes a single-pass transmembrane protein and is involved in regulating MC differentiation or immune responses (32).…”

Section: Discussionmentioning

confidence: 99%

“…Some miRNAs have been characterized as tumor suppressors in cancers and exerted roles via regulating their target genes (14,15). Wang et al speculated miR-125b as a target for septic cardiomyopathy for an increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves the overall survival of patients with sepsis (16). Restored miR-125a expression decreased the cell proliferation, cell cycle progression, and enhanced apoptosis by targeting ErbB in acute myeloid leukemia (17).…”

Section: Introductionmentioning

confidence: 99%

Silence of long noncoding RNA NEAT1 exerts suppressive effects on immunity during sepsis by promoting microRNA‐125‐dependent MCEMP1 downregulation

2019

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Accumulating studies have recognized microRNAs (miRs) and long noncoding RNAs (lncRNAs) as important molecules involved in the mediation of various biological processes, including innate immunity. In this study, we investigated a novel noncoding RNA regulatory circuitry in the immunity during sepsis. A cecal ligation and puncture‐induced sepsis mouse model was established to determine the expression of mast cell expression membrane protein 1 (MCEMP1). The RNA crosstalk among lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR‐125, and MCEMP1 was validated. Subsequently, the levels of lncRNA NEAT1, miR‐125, and MCEMP1 in T lymphocytes isolated from sepsis mice were up‐ or downregulated by exogenous transfection in an attempt to investigate their effects on the release of inflammatory factors, the expression of immunoglobulins, the activity of T cell subsets and natural killer (NK) cells, as well as T lymphocyte apoptosis. In sepsis mice, MCEMP1 was highly expressed and verified to be a target gene of miR‐125. RNA crosstalk experiment revealed that lncRNA NEAT1 directly inhibited miR‐125 to upregulate MCEMP1. We also observed that elevation of miR‐125, depletion of MCEMP1, or downregulation of lncRNA NEAT1 resulted in promoted T lymphocyte activity, immunoglobulin expression, and NK cell activity, and inhibited release of inflammatory factors and T lymphocyte apoptosis. Taken together, these findings provided evidence that the downregulation of lncRNA NEAT1 could promote miR‐125 to exert an inhibitory effect on the immunity in septic mice by suppressing MCEMP1, highlighting a potential target for the treatment of sepsis. © 2019 IUBMB Life, 2019

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MicroRNA-125b Prevents Cardiac Dysfunction in Polymicrobial Sepsis by Targeting TRAF6-Mediated Nuclear Factor κB Activation and p53-Mediated Apoptotic Signaling

Abstract: Increased myocardial miR-125b expression attenuates sepsis-induced cardiac dysfunction and improves survival. miR-125b may be a target for septic cardiomyopathy.

Cited by 88 publications

References 42 publications

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Endothelial microRNAs regulating the NF‐κB pathway and cell adhesion molecules during inflammation

Silence of long noncoding RNA NEAT1 exerts suppressive effects on immunity during sepsis by promoting microRNA‐125‐dependent MCEMP1 downregulation

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