Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Takahashi, Akiko; Okada, Ryo; Nagao, Koji; Kawamata, Yuka; Hanyu, Aki; Yoshimoto, Shin; Takasugi, Masaki; Watanabe, Sugiko; Kanemaki, Masato T.; Obuse, Chikashi; Hara, Eiji

doi:10.1038/ncomms15287

Cited by 579 publications

(523 citation statements)

References 70 publications

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“…Exosomes seem to play a part in maintaining cellular homeostasis by removing harmful cytoplasmic DNA from cells, as shown both in vitro and in vivo 44 . Inhibition of exosome release results in an accumulation of genomic DNA in the cell, which leads to apoptotic cell death 44 .…”

Section: Biogenesis Of Extracellular Vesiclesmentioning

confidence: 93%

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Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery

et al. 2017

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Urine is a valuable diagnostic medium and, with the discovery of urinary extracellular vesicles, is viewed as a dynamic bioactive fluid. Extracellular vesicles are lipid-enclosed structures that can be classified into three categories: exosomes, microvesicles (or ectosomes) and apoptotic bodies. This classification is based on the mechanisms by which membrane vesicles are formed: fusion of multivesicular bodies with the plasma membranes (exosomes), budding of vesicles directly from the plasma membrane (microvesicles) or those shed from dying cells (apoptotic bodies). During their formation, urinary extracellular vesicles incorporate various cell-specific components (proteins, lipids and nucleic acids) that can be transferred to target cells. The rigour needed for comparative studies has fueled the search for optimal approaches for their isolation, purification, and characterization. RNA, the newest extracellular vesicle component to be discovered, has received substantial attention as an extracellular vesicle therapeutic, and compelling evidence suggests that ex vivo manipulation of microRNA composition may have uses in the treatment of kidney disorders. The results of these studies are building the case that urinary extracellular vesicles act as mediators of renal pathophysiology. As the field of extracellular vesicle studies is burgeoning, this Review focuses on primary data obtained from studies of human urine rather than on data from studies of laboratory animals or cultured immortalized cells.

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Section: Biogenesis Of Extracellular Vesiclesmentioning

confidence: 93%

“…Inhibition of exosome release results in an accumulation of genomic DNA in the cell, which leads to apoptotic cell death 44 .…”

Section: Biogenesis Of Extracellular Vesiclesmentioning

confidence: 99%

Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery

et al. 2017

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“…As shown in Figure , EVs from male embryos at higher oxygen level contained higher level of NFE2L2 and SOD1 transcripts compared to those cultured under low oxygen level, which might be beneficial of development of embryos (Pavani et al, ). The role of EVs is not only in cell–cell communication (Saeed‐Zidane et al, ) but also in the removal of undesirable cellular molecules (Takahashi et al, ). Contrary to cellular expression, the NOTCH1 was increased in EVs derived from male embryos exposed to OS compared with female counterparts, which may indicate the selectivity of cargo molecules to be exported by EVs (Bhome et al, ; Hinger et al, ) to facilitate cell to cell communication or maintain of cellular homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of their size, EVs can be subdivided into apoptotic bodies (1,000–5,000 nm), microvesicles (100–1,000 nm), and exosomes (30–200 nm; Lawson et al, ; Sun et al, ; de la Torre Gomez, Goreham, Bech Serra, Nann & Kussmann, ). They carry a cargo of bioactive molecules such as DNA, RNAs, proteins to be transferred into the extracellular environment to maintain cellular homeostasis (Takahashi et al, ) and/or transfer genetic material to neighbor or distant recipient cells (Saeed‐Zidane et al, ). In addition, its cargo content varies depending on the cell origin (de la Torre Gomez et al, ), physiological status (Hung et al, ; Navakanitworakul et al, ), inflammation (Jolly, Thompson, & Winchester, ) and stress status (Beninson et al, ; Bewicke‐Copley et al, ) of the donor cells.…”

Section: Introductionmentioning

confidence: 99%

Sexual dimorphic expression and release of transcription factors in bovine embryos exposed to oxidative stress

Taqi

Saeed‐Zidane

Gebremedhn

et al. 2019

Molecular Reproduction Devel

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Sexually dimorphic differences in genome activity, which is orchestrated by transcription factors (TFs), could explain the differential response of male and female embryos to environmental stressors. To proof this hypothesis, the expression of cellular and extracellular TFs was investigated in male and female bovine embryos in vitro cultured either under low (5%) or high (20%) oxygen levels. The intracellular reactive oxygen species (ROS), total cell number, expression of nuclear factor (erythroid‐derived 2) factor 2 (NFE2L2), Krüppel‐like factor 4 (KLF4), notch receptor 1 (NOTCH1), E2F transcription factor 1 (E2F1), and SREBF2 along with extracellular vesicles (EVs) biogenesis genes were assessed at the blastocyst stage and their released EVs. Low blastocyst rate in both sexes due to oxidative stress (OS) was accompanied by increased ROS accumulation and reduced cell number in female embryos. The messenger RNA and protein levels of NFE2L2, as well as KLF4 expression, were higher in male embryos exposed to OS compared with female embryos. However, the expression of NOTCH1 and E2F1 was higher in female embryos cultured in high oxygen level. Male embryos exposed to OS released more EVs enriched with NFE2L2, superoxide dismutase 1, and NOTCH1 accompanied by elevated expression of EVs biogenesis genes. Accordingly, differential expression of TFs and their release into spent media could partially explain the sexual dimorphic response of bovine embryos to environmental stresses.

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“…The translational value of exosomal DNA in exosomes derived from tumors is very important for its potential usefulness as a circulating biomarker of metastasis and cancer in the early detection. It has been shown that there is an inverse correlation between the incidence of apoptosis and the levels of exosome secretion that contains DNA …”

Section: Oncogenic Roles Of Exosomes In Cancermentioning

confidence: 99%

Exosomes and cancer: From oncogenic roles to therapeutic applications

et al. 2019

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Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell‐to‐cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.

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Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Cited by 579 publications

References 70 publications

Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery

Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery

Sexual dimorphic expression and release of transcription factors in bovine embryos exposed to oxidative stress

Exosomes and cancer: From oncogenic roles to therapeutic applications

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