Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels

Kinoshita, Chisato; Aoyama, Koji; Matsumura, Nobuko; Kikuchi-Utsumi, Kazue; Watabe, Masahiko; Nakaki, Toshio

doi:10.1038/ncomms4823

Cited by 73 publications

(59 citation statements)

References 46 publications

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“…A total of 16 miRNAs were upregulated (bta‐let‐7c, bta‐miR‐23a, bta‐miR‐34a, bta‐miR‐96, bta‐miR‐98, bta‐miR‐182, bta‐miR‐204, bta‐miR‐211, bta‐miR‐221, bta‐miR‐224, bta‐miR‐301b, bta‐miR‐302d, bta‐miR‐449a, bta‐miR‐450a, bta‐miR‐454 and bta‐miR‐1224) while two miRNAs were downregulated (bta‐miR‐132, and bta‐miR‐210) in high compared to low oxygen tension. The miRNA‐96 regulates glutathione (GSH), which when inhibited causes an increase of GSH levels and increases the cell viability in neuronal mouse cells (Kinoshita et al, ). GSH is a nonenzymatic cellular antioxidant, which removes ROS excess by reducing peroxides and hydroperoxides in inactive products (Matos et al, ).…”

Section: Discussionmentioning

confidence: 99%

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

Andrade

Bomfim

Collado

et al. 2019

Molecular Reproduction Devel

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The biotechnology for in vitro embryo production is becoming increasingly popular, being applied to humans and domestic animals. Embryo development can be achieved with either 20% or 5% oxygen tension. The extracellular vesicles (EVs) are secreted by different cell types and carry bioactive materials. Our objective was to determine the secretion pattern and micro RNA (miRNA) contents of EVs released in the bovine embryo culture environment—embryo and cumulus cell monolayer—on Days 3 and 7 of in vitro culture under two different oxygen tensions: High (20%) and low (5%). The EVs were isolated from the medium and analyzed to determine size, concentration, and miRNA levels. EVs concentration in low oxygen tension increased on Day 3 and decreased on Day 7. Additionally, altered EV miRNAs derived from the embryo‐cumulus culture medium were predicted to regulate survival and proliferation‐related pathways on Days 3 and 7. Moreover, miR‐210 levels decreased in EVs isolated from the culture medium under high oxygen tension suggesting that this miRNA can be used as a marker for normoxia since it is associated with low oxygen tension. In summary, this study provides knowledge of the oxygen tension effects on EVs release and content, and potentially, on cell‐to‐cell communication during in vitro bovine embryo production.

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Section: Discussionmentioning

confidence: 99%

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

Andrade

Bomfim

Collado

et al. 2019

Molecular Reproduction Devel

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show abstract

“…(76) Kinoshita and colleagues (77) showed that miR-96-5p indirectly regulated glutathione (GSH) levels, a key antioxidant responsible for eliminating the damaging, oxidative stress-related reactive oxygen species (ROS). (78) Low levels of miR-96-5p reduced oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

Heilmeier

Hackl²,

Skalicky

et al. 2016

Journal of Bone and Mineral Research

118

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Standard DXA measurements, including Fracture Risk Assessment Tool (FRAX) scores, have shown limitations in assessing fracture risk in Type 2 Diabetes (T2D), underscoring the need for novel biomarkers and suggesting that other pathomechanisms may drive diabetic bone fragility. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues proportional to local disease severity and were recently found to be crucial to bone homeostasis and T2D. Here, we studied, if and which circulating miRNAs or combinations of miRNAs can discriminate best fracture status in a well-characterized study of diabetic bone disease and postmenopausal osteoporosis (n ¼ 80 postmenopausal women). We then tested the most discriminative and most frequent miRNAs in vitro. Using miRNA-qPCR-arrays, we showed that 48 miRNAs can differentiate fracture status in T2D women and that several combinations of four miRNAs can discriminate diabetes-related fractures with high specificity and sensitivity (area under the receiver-operating characteristic curve values [AUCs], 0.92 to 0.96; 95% CI, 0.88 to 0.98). For the osteoporotic study arm, 23 miRNAs were fracture-indicative and potential combinations of four miRNAs showed AUCs from 0.97 to 1.00 (95% CI, 0.93 to 1.00). Because a role in bone homeostasis for those miRNAs that were most discriminative and most present among all miRNA combinations had not been described, we performed in vitro functional studies in human adipose tissue-derived mesenchymal stem cells to investigate the effect of miR-550a-5p, miR-188-3p, and miR-382-3p on osteogenesis, adipogenesis, and cell proliferation. We found that miR-382-3p significantly enhanced osteogenic differentiation (p < 0.001), whereas miR-550a-5p inhibited this process (p < 0.001). Both miRNAs, miR-382-3p and miR-550a-5p, impaired adipogenic differentiation, whereas miR-188-3p did not exert an effect on adipogenesis. None of the miRNAs affected significantly cell proliferation. Our data suggest for the first time that miRNAs are linked to fragility fractures in T2D postmenopausal women and should be further investigated for their diagnostic potential and their detailed function in diabetic bone.

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“…To investigate the role of miR-23a-3p treatment on cerebral ischemia-reperfusion injury, the miR-23a-3p angomir (100 mM) (Kinoshita et al, 2014;Selvamani et al, 2012) was administrated via intracerebroventricular injection and the cerebral infarction volume was evaluated after 1 h of ischemia and 24 h of reperfusion by TTC staining. The results showed that miR-23a-3p angomir significantly reduced cerebral infarction volume, as compared with those in the MCAO group ( Fig.…”

Section: 2mentioning

confidence: 99%

MicroRNA-23a-3p attenuates oxidative stress injury in a mouse model of focal cerebral ischemia-reperfusion

et al. 2014

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Rhythmic oscillations of the microRNA miR-96-5p play a neuroprotective role by indirectly regulating glutathione levels

Cited by 73 publications

References 46 publications

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

Oxygen tension modulates extracellular vesicles and its miRNA contents in bovine embryo culture medium

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

MicroRNA-23a-3p attenuates oxidative stress injury in a mouse model of focal cerebral ischemia-reperfusion

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