Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.

Autor:	Vechetti IJ; Department of Nutrition and Health Sciences, College of Education and Human Sciences, University of Nebraska-Lincoln, Lincoln, NE, United States., Norrbom J; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden., Alkner B; Department of Orthopaedics, Eksjö, Region Jönköping County and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden., Hjalmarsson E; Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Palmcrantz A; Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Pontén E; Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; Department of Pediatric Orthopedic Surgery, Karolinska University Hospital, Stockholm, Sweden., Pingel J; Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark., von Walden F; Division of Pediatric Neurology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden., Fernandez-Gonzalo R; Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2022 Dec 21; Vol. 13, pp. 1072040. Date of Electronic Publication: 2022 Dec 21 (Print Publication: 2022).
DOI:	10.3389/fphys.2022.1072040
Abstrakt:	In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling ( n = 10; TD EX) or were enrolled as controls with no exercise ( n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD ( p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise ( p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Vechetti, Norrbom, Alkner, Hjalmarsson, Palmcrantz, Pontén, Pingel, von Walden and Fernandez-Gonzalo.)
Databáze:	MEDLINE
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