Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis

Wang, Xiaohong; Gu, Haitao; Qin, Dongze; Yang, Lei; Huang, Wei; Essandoh, Kobina; Wang, Yigang; Caldwell, Charles C.; Peng, Tianqing; Zingarelli, Basilia; Fan, Guo-Chang

doi:10.1038/srep13721

Cited by 263 publications

(237 citation statements)

References 47 publications

(126 reference statements)

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“…An example of this type of study would be the injection of extracellular vesicles isolated from either WT or miR-223-deficient mice into septic mice. With this technique, the authors were able to precisely determine how extracellular vesicle miR-223 impact the host response to sepsis (68). Here, had they been available and viable, the ideal control would have been NDMPs isolated from PS-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis

Johnson

Prakash

Rice

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Although advances in medical care have significantly improved sepsis survival, sepsis remains the leading cause of death in the ICU. This is likely due to a lack of complete understanding of the pathophysiologic mechanisms that lead to dysfunctional immunity. Neutrophil derived microparticles (NDMPs) have been shown to be the predominant microparticle present at infectious and inflamed foci in human models, however their effect on the immune response to inflammation and infection is sepsis has not been fully elucidated. As NDMPs may be a potential diagnostic and therapeutic target, we sought to determine the impact NDMPs on the immune response to a murine polymicrobial sepsis. We found that peritoneal neutrophil numbers, bacterial loads, and NDMPs were increased in our abdominal sepsis model. When NDMPs were injected into septic mice, we observed increased bacterial load, decreased neutrophil recruitment, increased expression of IL-10 and worsened mortality. Furthermore, the NDMPs express phosphatidylserine and are ingested by F4/80 macrophages via a Tim-4 and MFG-E8 dependent mechanism. Finally, upon treatment, NDMPs decrease macrophage activation, increase IL-10 release and decrease macrophage numbers. Altogether, these data suggest that NDMPs enhance immune dysfunction in sepsis by blunting the function of neutrophils and macrophages, two key cell populations involved in the early immune response to infection.

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Section: Discussionmentioning

confidence: 99%

Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis

Johnson

Prakash

Rice

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…This novel mechanism of miRNA transfer constitutes an important element of intracellular communication. Very recently, our lab has reported that stem cell-derived exosomal miR-223 significantly suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) by targeting Sema3A and STAT3 in macrophages of septic model (10). Similarly, another study showed that miR-155 and miR-146a, present in dendritic cell-derived exosomes, were passed between immune cells in vivo (11).…”

Section: Mirna Biogenesis and Mechanism Of Actionmentioning

confidence: 99%

MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response

Essandoh

Li²,

Huo³

et al. 2016

Shock

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477

385

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Monocytes and macrophages are important components of the immune system, specialized in either removing pathogens as part of innate immunity or contributing to adaptive immunity through antigen presentation. Essential to such functions is classical activation (M1) and alternative activation (M2) of macrophages. M1 polarization of macrophages is characterized by production of pro-inflammatory cytokines, antimicrobial and tumoricidal activity, whereas M2 polarization of macrophages is linked to immunosuppression, tumorigenesis, wound repair and elimination of parasites. MiRNAs are small non-coding RNAs with the ability to regulate gene expression and network of cellular processes. A number of studies have determined miRNA expression profiles in M1 and M2 polarized human and murine macrophages using microarray and RT-qPCR arrays techniques. More specifically, miR-9, miR-127, miR-155 and miR-125b have been shown to promote M1 polarization while miR-124, miR-223, miR-34a, let-7c, miR-132, miR-146a and miR-125a-5p induce M2 polarization in macrophages by targeting various transcription factors and adaptor proteins. Further, M1 and M2 phenotypes play distinctive roles in cell growth and progression of inflammation-related diseases such as sepsis, obesity, cancer and multiple sclerosis. Hence, miRNAs that modulate macrophage polarization may have therapeutic potential in the treatment of inflammation-related diseases. This review highlights recent findings in miRNA expression profiles in polarized macrophages from murine and human sources, and summarizes how these miRNAs regulate macrophage polarization. Lastly, therapeutic potential of miRNAs in inflammation-related diseases through modulation of macrophage polarization is also discussed.

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“…The mechanism for MSC-induced protection is unknown; however, it has been demonstrated that MSCs release exosomes during sepsis that harbor miR-223 which is cardioprotective in the CLP-induced sepsis model [100]. This effect may be related to the anti-inflammatory effects of miR-223 which reduces the expression of proinflammatory cytokines.…”

Section: Mitochondrial Dysfunction Can Lead To Permanent Muscle Loss mentioning

confidence: 99%

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

Wong

2017

Mol Diagn Ther

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Sepsis remains one of the leading causes of death in the United States and it is expected to get worse as the population ages. Moreover, the standard of care, which recommends aggressive treatment with appropriate antibiotics, has led to an increase in multiple drug resistant organisms (MDROs). There is a dire need for the development of new antibiotics, improved antibiotic stewardship and therapies that treat the host response. Development of new sepsis therapeutics has been a disappointment as no drugs are currently approved to treat the various complications from sepsis. Much of the failure has been blamed on animal models that do not accurately reflect the course of the disease. However, recent improvements in metabolomic, transcriptomic, genomic and proteomic platforms have allowed for a broad spectrum look at molecular changes in the host response using clinical samples. Integration of these multi-omic data sets allows researchers to perform systems biology approaches to identify novel pathophysiology of the disease. In this review, we will highlight what is currently known about sepsis and how integrative omics has identified new diagnostic and predictive models of sepsis as well as novel mechanisms. These changes may improve patient care as well as guide future preclinical analysis of sepsis.

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Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis

Cited by 263 publications

References 47 publications

Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis

Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis

MiRNA-Mediated Macrophage Polarization and its Potential Role in the Regulation of Inflammatory Response

Early Diagnosis of Sepsis: Is an Integrated Omics Approach the Way Forward?

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