1. Extracellular vesicle miR-206 improves chronic binge alcohol-mediated decreased myoblast differentiation in SIV-infected female macaques.
- Author
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Bourgeois BL, Gallegos EM, Levitt DE, Bergeaux PJ, Molina PE, and Simon L
- Subjects
- Animals, Female, Macaca mulatta, Simian Immunodeficiency Virus drug effects, Muscle, Skeletal metabolism, Muscle, Skeletal drug effects, Muscle, Skeletal pathology, Muscle Fibers, Skeletal metabolism, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal virology, Muscle Fibers, Skeletal pathology, Ethanol pharmacology, Ethanol administration & dosage, MicroRNAs genetics, MicroRNAs metabolism, Extracellular Vesicles metabolism, Cell Differentiation drug effects, Simian Acquired Immunodeficiency Syndrome metabolism, Simian Acquired Immunodeficiency Syndrome genetics, Simian Acquired Immunodeficiency Syndrome drug therapy, Simian Acquired Immunodeficiency Syndrome pathology, Simian Acquired Immunodeficiency Syndrome virology, Binge Drinking metabolism, Binge Drinking genetics, Binge Drinking pathology, Binge Drinking drug therapy, Myoblasts metabolism, Myoblasts drug effects
- Abstract
Alcohol misuse in people with human immunodeficiency virus (HIV) (PWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with increased physical frailty and impaired functional skeletal muscle mass, respectively. Previous studies by our group demonstrate that muscle-enriched microRNAs (myomiRs) are differentially expressed in skeletal muscle (SKM) from CBA-administered SIV-infected male macaques and their altered expression contributes to impaired differentiation of SKM stem cells or myoblasts. MicroRNAs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular communication. The present study tested the hypothesis that EV-mediated delivery of miR-206 can ameliorate CBA-mediated decreases in myoblast differentiation. Myoblasts were isolated from SKM of female SIV-infected, antiretroviral therapy-treated macaques that received either CBA (2.5 g/kg/day, CBA/SIV) or water (VEH/SIV) for 14.5 mo. Myotube and myotube-derived EV myomiR expression, including miR-206, was lower in the CBA/SIV group. Overexpression of miR-206 decreased histone deacetylase 4 ( HDAC4 ) and paired box 7 ( PAX7 ) expression in myotubes and increased fusion index, a differentiation index, in CBA/SIV-derived myotubes. Similarly, EV-mediated delivery of miR-206 increased both fusion index and myotube density of CBA/SIV-derived myoblasts. These results support the potential therapeutic utility of EVs in delivering myomiRs to improve SKM stem cell differentiation. NEW & NOTEWORTHY Alcohol decreases skeletal muscle myoblast differentiation into myotubes, which is associated with decreased expression of microRNA-206. We show that delivering exogenous miR-206 in plasma-derived extracellular vesicles (EVs) to myoblasts derived from alcohol-administered animals increases myotube differentiation. These results support the potential therapeutic utility of EVs in delivering muscle-enriched microRNAs to improve skeletal muscle stem cell differentiation.
- Published
- 2024
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