Myotube-derived exosomal miRNAs downregulate Sirtuin1 in myoblasts during muscle cell differentiation

Autor: Etienne Lefai, Audrey Jalabert, Hubert Vidal, Sophie Rome, Sandra Pesenti, Karim Chikh, Elizabeth Errazuriz, Vanessa Euthine, Alexis Forterre, Aurélie Granjon
Přispěvatelé: Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Fondation pour la Recherche Medicale (FRM ), Association Francaise de recherche sur les Myopathies (AFM ), Association Francaise de Diabetologie (SDF ), INRA-specific grant (ANSSD), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Jazyk: angličtina
Rok vydání: 2014
Předmět:
MicroRNAs/*biosynthesis/classification/genetics
[SDV]Life Sciences [q-bio]
Muscle Fibers
Skeletal

Biology
Skeletal/metabolism
Exosomes
Exosome
Muscle Fibers
Myoblasts
03 medical and health sciences
Mice
0302 clinical medicine
Report
medicine
Cell Differentiation/*genetics
Sirtuins
Myocyte
Animals
Homeostasis
Sirtuins/*biosynthesis/genetics
Developmental
Muscle
Skeletal

Molecular Biology
030304 developmental biology
0303 health sciences
Myogenesis
Muscle cell differentiation
Wnt signaling pathway
Gene Expression Regulation
Developmental

Skeletal muscle
Cell Differentiation
Cell Biology
Microvesicles
Cell biology
MicroRNAs
Exosomes/metabolism
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
Muscle
Myoblasts/cytology/*metabolism
Skeletal/growth & development/metabolism
C2C12
Developmental Biology
Zdroj: Cell Cycle
Cell Cycle, Taylor & Francis, 2014, 13 (1), pp.78-89. ⟨10.4161/cc.26808⟩
ISSN: 1538-4101
1551-4005
DOI: 10.4161/cc.26808⟩
Popis: International audience; It has recently been established that exosomes can mediate intercellular cross-talk under normal and pathological conditions through the transfer of specific miRNAs. As muscle cells secrete exosomes, we addressed the question of whether skeletal muscle (SkM) exosomes contained specific miRNAs, and whether they could act as "endocrine signals" during myogenesis. We compared the miRNA repertoires found in exosomes released from C2C12 myoblasts and myotubes and found that 171 and 182 miRNAs were exported into exosomes from myoblasts and myotubes, respectively. Interestingly, some miRNAs were expressed at higher levels in exosomes than in their donor cells and vice versa, indicating a selectivity in the incorporation of miRNAs into exosomes. Moreover miRNAs from C2C12 exosomes were regulated during myogenesis. The predicted target genes of regulated exosomal miRNAs are mainly involved in the control of important signaling pathways for muscle cell differentiation (e.g., Wnt signaling pathway). We demonstrated that exosomes from myotubes can transfer small RNAs (C. elegans miRNAs and siRNA) into myoblasts. Moreover, we present evidence that exosome miRNAs secreted by myotubes are functionally able to silence Sirt1 in myoblasts. As Sirt1 regulates muscle gene expression and differentiation, our results show that myotube-exosome miRNAs could contribute to the commitment of myoblasts in the process of differentiation. Until now, myokines in muscle cell secretome provided a conceptual basis for communication between muscles. Here, we show that miRNA exosomal transfer would be a powerful means by which gene expression is orchestrated to regulate SkM metabolic homeostasis.
Databáze: OpenAIRE