MicroRNA cargo of extracellular vesicles released by skeletal muscle fibro-adipogenic progenitor cells is significantly altered with disuse atrophy and IL-1ß deficiency.
Physiol Genomics
; 54(8): 296-304, 2022 08 01.
Article
in En
| MEDLINE
| ID: mdl-35759450
ABSTRACT
Fibro-adipogenic progenitor cells (FAPs) are a population of stem cells in skeletal muscle that play multiple roles in muscle repair and regeneration through their complex secretome; however, it is not well understood how the FAP secretome is altered with muscle disuse atrophy. Previous work suggests that the inflammatory cytokine IL-1ß is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1ß secretion are also known to stimulate the release of extracellular vesicles (EVs). Here, we examined the microRNA (miRNA) cargo of FAP-derived, platelet-derived growth factor receptor A (PDGFRα+) EVs from hindlimb muscles of wild-type and IL-1ß KO mice after 14 days of single-hindlimb immobilization. Hindlimb muscles were isolated from mice following the immobilization period, and PDGFRα+ extracellular vesicles were isolated using size-exclusion chromatography and immunoprecipitation. Microarrays were performed to detect changes in miRNAs with unloading and IL-1ß deficiency. Results indicate that the PDGFRα+, FAP-derived EVs show a significant increase in miRNAs, such as miR-let-7c, miR-let-7b, miR-181a, and miR-124. These miRNAs have previously been demonstrated to play important roles in cellular senescence and muscle atrophy. Furthermore, the expression of these same miRNAs was not significantly altered in FAP-derived EVs isolated from the immobilized IL-1ß KO. These data suggest that disuse-related activation of IL-1ß can mediate the miRNA cargo of FAP-derived EVs, contributing directly to the release of senescence- and atrophy-related miRNAs. Therapies targeting FAPs in settings associated with muscle disuse atrophy may therefore have the potential to preserve muscle function and enhance muscle recovery.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muscular Disorders, Atrophic
/
MicroRNAs
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Interleukin-1beta
/
Extracellular Vesicles
Limits:
Animals
Language:
En
Journal:
Physiol Genomics
Journal subject:
BIOLOGIA MOLECULAR
Year:
2022
Type:
Article
Affiliation country:
Georgia