Genomics

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Secreted miRNAs from primary myocytes


ABSTRACT: Amyotrophic lateral sclerosis (ALS) is the most common adult-onset paralytic disorder, characterized primarily by a progressive loss of motor neurons in whose degeneration skeletal muscle involvement has been demonstrated. Skeletal muscle is a plastic tissue that responds to insults through proliferation and differentiation of satellite cells. The process of skeletal muscle degeneration and regeneration are finely regulated by signals that regulate satellite cell proliferation and differentiation. It is known that satellite cell differentiation is impaired in ALS, but little is known about the involvement of miRNAs and their role in intercellular communication in skeletal muscle in ALS. Here we demonstrated impaired differentiation of satellite cells derived from ALS mice related to the impairment of myogenic p38MAPK and PKA/pCREB signaling pathways that can be regulated by miR-882 and -134-5p. These miRNAs participate in autocrine signaling in association with miR-26a-5p, that, secreted from WT and captured by ALS myoblasts, enhances ALS-related myoblast differentiation by repressing Smad4-related signals. These findings underscore the urgency of better understanding the role of intercellular communication and the molecular mechanisms underlying ALS pathogenesis and progression. They also suggest that miRNAs could be targeted as potential therapeutic agents to enhance myofiber regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE274702 | GEO | 2025/07/02

REPOSITORIES: GEO

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