Characterization of a novel microRNA, miR-188, elevated in serum of muscular dystrophy dog model

Shibasaki, Hiroyuki; Imamura, Michihiro; Arima, Sayuri; Tanihata, Jun; Kuraoka, Mutsuki; Matsuzaka, Yasunari; Uchiumi, Fumiaki; Tanuma, Sei Ichi; Takeda, Shin’ichi

doi:10.1371/journal.pone.0211597

Cited by 13 publications

(10 citation statements)

References 26 publications

(26 reference statements)

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“…Whether these above molecules can participate in age-related bone-muscle crosstalk or not requires further research. Furthermore, we were inspired to investigate whether miR-188, which appears increased in aging BMSCs, can be released through EVs to regulate aging muscle phenotype, since miR-188 was reportedly elevated in a muscular dystrophy dog model ( Li et al, 2015 ; Shibasaki et al, 2019 ). Zacharewicz et al (2014 , 2020) reported that miR-99b displays a negative age-dependent association with protein synthesis in skeletal muscle.…”

Section: Ev-micrornas Of Bone Cells Engaged In Bone-muscle Crosstalkmentioning

confidence: 99%

Bone and Muscle Crosstalk in Aging

Hou

et al. 2020

Front. Cell Dev. Biol.

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Osteoporosis and sarcopenia are two age-related diseases that affect the quality of life in the elderly. Initially, they were thought to be two independent diseases; however, recently, increasing basic and clinical data suggest that skeletal muscle and bone are both spatially and metabolically connected. The term “osteosarcopenia” is used to define a condition of synergy of low bone mineral density with muscle atrophy and hypofunction. Bone and muscle cells secrete several factors, such as cytokines, myokines, and osteokines, into the circulation to influence the biological and pathological activities in local and distant organs and cells. Recent studies reveal that extracellular vesicles containing microRNAs derived from senescent skeletal muscle and bone cells can also be transported and aid in regulating bone-muscle crosstalk. In this review, we summarize the age-related changes in the secretome and extracellular vesicle-microRNAs secreted by the muscle and bone, and discuss their interactions between muscle and bone cells during aging.

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Section: Ev-micrornas Of Bone Cells Engaged In Bone-muscle Crosstalkmentioning

confidence: 99%

Bone and Muscle Crosstalk in Aging

Hou

et al. 2020

Front. Cell Dev. Biol.

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“…Circulating exosomal miRNA in blood is linked to disease condition. For example, miR-126 and miR-223 are known markers of type 2 diabetes in human [49] and elevation of miR-188 in sera of muscular dystrophy dog [50]. Furthermore, adipose tissue is a major source of circulating exosomal miRNAs [38].…”

Section: Possible Roles In the Expansion Of Adipocytes In Tissues Thrmentioning

confidence: 99%

Immature adipocyte‐derived exosomes inhibit expression of muscle differentiation markers

et al. 2021

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Exosomes are released from a variety of cells to communicate with recipient cells. Exosomes contain microRNAs (miRNAs), which are noncoding RNAs that suppress target genes. Our previous proteomic study (FEBS Open Bio 2016, 6, 816–826) demonstrated that 3T3‐L1 adipocytes secrete exosome components as well as growth factors, inspiring us to investigate what type of miRNA is involved in adipocyte‐secreted exosomes and what functions they carry out in recipient cells. Here, we profiled miRNAs in 3T3‐L1 adipocyte‐secreted exosomes and revealed suppression of muscle differentiation by adipocyte‐derived exosomes. Through our microarray analysis, we detected over 300 exosomal miRNAs during adipocyte differentiation. Exosomal miRNAs present during adipocyte differentiation included not only pro‐adipogenic miRNAs but also miRNAs associated with muscular dystrophy. Gene ontology analysis predicted that the target genes of miRNAs are associated primarily with transcriptional regulation. To further investigate whether adipocyte‐secreted exosomes regulate the expression levels of genes involved in muscle differentiation, we treated cultured myoblasts with adipocyte‐derived exosome fractions. Intriguingly, the expression levels of myogenic regulatory factors, Myog and Myf6, and other muscle differentiation markers, myosin heavy‐chain 3 and insulin‐like growth factor 2, were significantly downregulated in myoblasts treated with adipocyte‐derived exosomes. Immature adipocyte‐derived exosomes exhibited a stronger suppressive effect than mature adipocyte‐derived exosomes. Our results suggest that adipocytes suppress the expression levels of muscle differentiation‐associated genes in myoblasts via adipocyte‐secreted exosomes containing miRNAs.

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“…Canine X-linked muscular dystrophy in Japan (CXMD J ), a beagle-based dystrophic dog, is a midsize mammalian translational model of DMD ( Supplementary Fig. S1a) that mimics the human DMD phenotype more closely than the widely used dystrophin-deficient rodent models [13] and has been used to investigate molecular mechanisms triggering the physiopathological modifications in DMD [14][15][16][17][18][19]. The CXMD J dog model harbors a splice site mutation in intron 6 of the DMD gene on the X chromosome, which causes the loss of exon 7 and a disrupted reading frame in DMD mRNA (Supplementary Fig.…”

Section: Introductionmentioning

confidence: 99%

Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides

Tone

Mamchaoui

Tsoumpra

et al. 2021

Nucleic Acid Therapeutics

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Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease caused by frameshift or nonsense mutations in the DMD gene, resulting in the loss of dystrophin from muscle membranes. Exon skipping using splice-switching oligonucleotides (SSOs) restores the reading frame of DMD pre-mRNA by generating internally truncated but functional dystrophin protein. To potentiate effective tissue-specific targeting by functional SSOs, it is essential to perform accelerated and reliable in vitro screening-based assessment of novel oligonucleotides and drug delivery technologies, such as cell-penetrating peptides, before their in vivo pharmacokinetic and toxicity evaluation. We have established novel canine immortalized myoblast lines by transducing murine cyclin-dependent kinase-4 and human telomerase reverse transcriptase genes into myoblasts isolated from beagle-based wild-type or canine X-linked muscular dystrophy in Japan (CXMD J) dogs. These myoblast lines exhibited improved myogenic differentiation and increased proliferation rates compared with passage-15 primary parental myoblasts, and their potential to differentiate into myotubes was maintained in later passages. Using these dystrophin-deficient immortalized myoblast lines, we demonstrate that a novel cell-penetrating peptide (Pip8b2)-conjugated SSO markedly improved multiexon skipping activity compared with the respective naked phosphorodiamidate morpholino oligomers. In vitro screening using immortalized canine cell lines will provide a basis for further pharmacological studies on drug delivery tools.

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Characterization of a novel microRNA, miR-188, elevated in serum of muscular dystrophy dog model

Cited by 13 publications

References 26 publications

Bone and Muscle Crosstalk in Aging

Bone and Muscle Crosstalk in Aging

Immature adipocyte‐derived exosomes inhibit expression of muscle differentiation markers

Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides

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