Brown Fat-Derived Exosomes: Small Vesicles with Big Impact

Chen, Yong; Pfeifer, Alexander

doi:10.1016/j.cmet.2017.03.012

Cited by 35 publications

(30 citation statements)

References 10 publications

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“…miRNAs can directly interact with complementary regions in the 3′ untranslated region of target mRNAs, thereby regulating their rate of promoting their degradation . In addition to functioning within cells, miRNAs have also recently been shown to be secreted extracellularly in exosomes, allowing for their transfer to proximal or distal cells where they can regulate gene expression . One recent study found that exosomes from patients with type 2 diabetes exhibit elevated levels of miR‐20b‐5p and that this miRNA impairs insulin activity within skeletal muscle .…”

Section: Introductionmentioning

confidence: 99%

Circulating Exosomal miR‐20b‐5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes‐Associated Impaired Wound Healing

Xiong

Chen

Yan

et al. 2019

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At present, developing therapeutic strategies to improve wound healing in individuals with diabetes remains challenging. Exosomes represent a promising nanomaterial from which microRNAs (miRNAs) can be isolated. These miRNAs have the potential to exert therapeutic effects, and thus, determining the potential therapeutic contributions of specific miRNAs circulating in exosomes is of great importance. In the present study, circulating exosomal miRNAs are identified in diabetic patients and assessed for their roles in the context of diabetic wound healing. A significant upregulation of miR‐20b‐5p is observed in exosomes isolated from patients with type 2 diabetes mellitus (T2DM), and this miRNA is able to suppress human umbilical vein endothelial cell angiogenesis via regulation of Wnt9b/β‐catenin signaling. It is found that the application of either miR‐20b‐5p or diabetic exosomes to wound sites is sufficient to slow wound healing and angiogenesis. In diabetic mice, it is found that knocking out miR‐20b‐5p significantly enhances wound healing and promotes wound angiogenesis. Together, these findings thus provide strong evidence that miR‐20b‐5p is highly enriched in exosomes from patients with T2DM and can be transferred to cells of the vascular endothelium, where it targets Wnt9b signaling to negatively regulate cell functionality and angiogenesis.

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Section: Introductionmentioning

confidence: 99%

Circulating Exosomal miR‐20b‐5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes‐Associated Impaired Wound Healing

Xiong

Chen

Yan

et al. 2019

Small

149

107

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show abstract

“…Exosomes are membrane‐bound phospholipid vesicles (40–150 nm in diameter) of endocytic origin (Chen, & Pfeifer, 2017; Guo, Tao et al., 2016; Im et al., 2014). Exosomes are intracellularly secreted by endocytic invagination of mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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“…Thus, many researchers became interested in treating obesity and diabetes by activating brown adipose tissues or beige adipoctyes (28). Brown adipose tissues are also known to release EVs, which could be biomarkers of brown adipose tissue activity and therapeutic agents for obesity and related diseases (29).…”

Section: Introductionmentioning

confidence: 99%

Cell reprogramming using extracellular vesicles from differentiating stem cells into white/beige adipocytes

et al. 2020

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Stem cell–derived extracellular vesicles (EVs) offer alternative approaches to stem cell–based therapy for regenerative medicine. In this study, stem cell EVs derived during differentiation are developed to use as cell-free therapeutic systems by inducing tissue-specific differentiation. EVs are isolated from human adipose-derived stem cells (HASCs) during white and beige adipogenic differentiation (D-EV and BD-EV, respectively) via tangential flow filtration. D-EV and BD-EV can successfully differentiate HASCs into white and beige adipocytes, respectively. D-EV are transplanted with collagen/methylcellulose hydrogels on the backs of BALB/c mice, and they produce numerous lipid droplets in injected sites. Treatments of BD-EV attenuate diet-induced obesity through browning of adipose tissue in mice. Furthermore, high-fat diet–induced hepatic steatosis and glucose tolerance are improved by BD-EV treatment. miRNAs are responsible for the observed effects of BD-EV. These results reveal that secreted EVs during stem cell differentiation into white adipocytes or beige adipocytes can promote cell reprogramming.

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Brown Fat-Derived Exosomes: Small Vesicles with Big Impact

Cited by 35 publications

References 10 publications

Circulating Exosomal miR‐20b‐5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes‐Associated Impaired Wound Healing

Circulating Exosomal miR‐20b‐5p Inhibition Restores Wnt9b Signaling and Reverses Diabetes‐Associated Impaired Wound Healing

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

Cell reprogramming using extracellular vesicles from differentiating stem cells into white/beige adipocytes

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