MicroRNA cargo of extracellular vesicles released by skeletal muscle fibro-adipogenic progenitor cells is significantly altered with disuse atrophy and IL-1β deficiency.

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-1β is increased in FAPs with disuse and denervation. Inflammasome activation and IL-1β 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-1β 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-1β 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-1β KO. These data suggest that disuse-related activation of IL-1β 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.

• Authors: Emily Parker, Bharati Mendhe, Ling Ruan, Brendan Marshall, Wenbo Zhi, Yutao Liu, Sadanand Fulzele, Yao Liang Tang, Meghan McGee-Lawrence, Tae Jin Lee, Ashok Sharma, Maribeth Johnson, Jie Chen, Mark W Hamrick
• Journal: Physiological genomics (Physiol Genomics) Vol. 54 Issue 8 Pg. 296-304 (08 01 2022) ISSN: 1531-2267 [Electronic] United States
• PMID: 35759450 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• IL1B protein, mouse
• Interleukin-1beta
• MicroRNAs
• Receptor, Platelet-Derived Growth Factor alpha

Topics

• Animals
• Extracellular Vesicles (metabolism)
• Interleukin-1beta (metabolism)
• Mice
• MicroRNAs (genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Muscular Disorders, Atrophic (metabolism)
• Receptor, Platelet-Derived Growth Factor alpha (metabolism)
• Stem Cells (metabolism)