Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application

Katsuda, Takeshi; Ikeda, Shingo; Yoshioka, Yusuke; Kosaka, Nobuyoshi; Kawamata, Masayuki; Ochiya, Takahiro

doi:10.1515/hsz-2013-0222

Cited by 11 publications

(8 citation statements)

References 69 publications

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“…Such miRNAs may be secreted by a range of cells, such as immune cells (164), stem cells (195), blood cells (196) or adipocytes (192, 197), and growing evidence indicates that they may have important physiological roles [reviewed in Refs. (198–202)]. At least for some cell types, miRNAs may be transferred within EVs to neighbouring cells, where they alter the gene expression and phenotype of the recipient cells.…”

Section: Molecular Properties Of Evsmentioning

confidence: 99%

Biological properties of extracellular vesicles and their physiological functions

Yáñez-Mó

Siljander

Andreu

et al. 2015

J of Extracellular Vesicle

4,436

3,287

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In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

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Section: Molecular Properties Of Evsmentioning

confidence: 99%

Biological properties of extracellular vesicles and their physiological functions

Yáñez-Mó

Siljander

Andreu

et al. 2015

J of Extracellular Vesicle

4,436

3,287

View full text Add to dashboard Cite

show abstract

“…The ability of exosomes to incorporate and transfer miRNAs indicates their ability to influence the physiological behavior of recipient cells [ 28 , 29 ]. They also have important roles in various biological processes [ 30–33 ], including cancer progression, immune regulation and tissue repair. However, their roles in bone remodeling have not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity

et al. 2016

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MicroRNAs have an important role in bone homeostasis. However, the detailed mechanism of microRNA-mediated intercellular communication between bone cells remains elusive. Here, we report that osteoclasts secrete microRNA-enriched exosomes, by which miR-214 is transferred into osteoblasts to inhibit their function. In a coculture system, inhibition of exosome formation and secretion prevented miR-214 transportation. Exosomes specifically recognized osteoblasts through the interaction between ephrinA2 and EphA2. In osteoclast-specific miR-214 transgenic mice, exosomes were secreted into the serum, and miR-214 and ephrinA2 levels were elevated. Therefore, these exosomes have an inhibitory role in osteoblast activity. miR-214 and ephrinA2 levels in serum exosomes from osteoporotic patients and mice were upregulated substantially. These exosomes may significantly inhibit osteoblast activity. Inhibition of exosome secretion via Rab27a small interfering RNA prevented ovariectomized-induced osteoblast dysfunction in vivo. Taken together, these findings suggest that exosome-mediated transfer of microRNA plays an important role in the regulation of osteoblast activity. Circulating miR-214 in exosomes not only represents a biomarker for bone loss but could selectively regulate osteoblast function.

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“…16–19 Furthermore, extracellular/circulating miRNAs has been found to have active roles in cell–cell communication, intercellular transport, targeting of gene expression in recipient cells and regulation of the immune system, among others. 10,20,21 While evidence for a functional, endocrine/paracrine-like role for extracellular miRNAs in metabolically involved tissues is just emerging, 22 the potential for endurance exercise-derived exosomes (which contain miRNAs among other ‘exerkines’) to treat metabolic diseases such as obesity and type 2 diabetes has been recently highlighted. 23 …”

Section: Introductionmentioning

confidence: 99%

Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk

et al. 2017

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BACKGROUND/OBJECTIVES Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-cell function in obese non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors. SUBJECTS/METHODS Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1–3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N = 11) or without (CON, N = 11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis. RESULTS Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI, and other cardiometabolic risk factors. CONCLUSIONS These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a ‘comprehensive’ weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.

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Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application

Cited by 11 publications

References 69 publications

Biological properties of extracellular vesicles and their physiological functions

Biological properties of extracellular vesicles and their physiological functions

Osteoclast-derived microRNA-containing exosomes selectively inhibit osteoblast activity

Gastric bypass surgery with exercise alters plasma microRNAs that predict improvements in cardiometabolic risk

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