Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage

Goulielmaki, Evi; Ιωαννίδου, Άννα; Tsekrekou, Maria; Stratigi, Kalliopi; Poutakidou, Ioanna K.; Gkirtzimanaki, Katerina; Aivaliotis, Michalis; Evangelou, Konstantinos; Altmüller, Janine; Gorgoulis, Vassilis G.; Chatzinikolaou, Georgia; Garinis, George A.

doi:10.1038/s41467-019-13894-9

Cited by 53 publications

(39 citation statements)

References 102 publications

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“…However, another study reported that EVs from LPS-induced macrophages failed to influence glucose uptake and fat storage in adipocytes but were able to up-regulate inflammation and carbohydrate catabolism related genes such as CXCL5, SOD, C3, and CD34 in adipocytes 87 . Additionally, macrophages derived from mice with knockout of Ercc1 , a highly conserved endonuclease complex required for lesion excision in nucleotide excision repair, release EVs to induce glucose transporter type-1 (GLUT-1) expression in pancreatic cells, further leading to hyperglycemia and inflammation in primary pancreatic cells 88 . Overall, these findings collectively verified that Mφ-EVs promote metabolic diseases development by modulating glucose and lipid metabolism pathways.…”

Section: Pathological Roles Of Mφ-evs In Diseasementioning

confidence: 99%

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

et al. 2020

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Macrophages (Mφ) are primary innate immune cells that exhibit diverse functions in response to different pathogens or stimuli, and they are extensively involved in the pathology of various diseases. Extracellular vesicles (EVs) are small vesicles released by live cells. As vital messengers, macrophage-derived EVs (Mφ-EVs) can transfer multiple types of bioactive molecules from macrophages to recipient cells, modulating the biological function of recipient cells. In recent years, Mφ-EVs have emerged as vital mediators not only in the pathology of multiple diseases such as inflammatory diseases, fibrosis and cancers, but also as mediators of beneficial effects in immunoregulation, cancer therapy, infectious defense, and tissue repair. Although many investigations have been performed to explore the diverse functions of Mφ-EVs in disease pathology and intervention, few studies have comprehensively summarized their detailed biological roles as currently understood. In this review, we briefly introduced an overview of macrophage and EV biology, and primarily focusing on current findings and future perspectives with respect to the pathological and therapeutic effects of Mφ-EVs in various diseases.

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Section: Pathological Roles Of Mφ-evs In Diseasementioning

confidence: 99%

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

et al. 2020

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“…The consequences of the accumulation of DNA damages and somatic mutations are tissue-specific. In particular, the damage in macrophage DNA enhances inflammation [ 97 ], in neurons, it leads to cognitive impairment [ 98 ], in osteoprogenitor cells, it causes bone loss [ 99 ]. It is worth highlighting the accumulation of DNA damage and mutations in stem cells, as this influences their regenerative potential and creates a risk of tumor stem cells [ 100 ].…”

Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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“…Bacterial and parasitic infections also affect exosome production and secretion [67,68], while metabolic dysfunction due to abiotic stress can also lead to exosomal changes. For example, environmental stresses, including ionizing radiation, can alter exosome secretion, composition and function [39,[69][70][71][72].…”

Section: Regulation and Functionmentioning

confidence: 99%

Exosome: A New Player in Translational Nanomedicine

Aheget

Tristán‐Manzano

Mazini

et al. 2020

JCM

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Summary: Exosomes are extracellular vesicles released by the vast majority of cell types both in vivo and ex vivo, upon the fusion of multivesicular bodies (MVBs) with the cellular plasma membrane. Two main functions have been attributed to exosomes: their capacity to transport proteins, lipids and nucleic acids between cells and organs, as well as their potential to act as natural intercellular communicators in normal biological processes and in pathologies. From a clinical perspective, the majority of applications use exosomes as biomarkers of disease. A new approach uses exosomes as biologically active carriers to provide a platform for the enhanced delivery of cargo in vivo. One of the major limitations in developing exosome-based therapies is the difficulty of producing sufficient amounts of safe and efficient exosomes. The identification of potential proteins involved in exosome biogenesis is expected to directly cause a deliberate increase in exosome production. In this review, we summarize the current state of knowledge regarding exosomes, with particular emphasis on their structural features, biosynthesis pathways, production techniques and potential clinical applications.

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Tissue-infiltrating macrophages mediate an exosome-based metabolic reprogramming upon DNA damage

Cited by 53 publications

References 102 publications

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

Genome-Protecting Compounds as Potential Geroprotectors

Exosome: A New Player in Translational Nanomedicine

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