Abstract
Cachexia is a prevalent syndrome in advanced cancer characterized by skeletal muscle atrophy. Impaired muscle regeneration exacerbates the loss of muscle mass. However, the mechanism underlying cachectic impairments in muscle regeneration remains unclear. Previous research revealed that P4HB accumulates in cachexia muscle. In this study, we explored the role of P4HB in muscle regeneration. We induced muscle injury in cachectic mice to demonstrate the impairment of muscle regeneration. Subsequently, we used inducible overexpression cell lines and muscle-specific knockout mice to elucidate the inhibitory role of P4HB in muscle regeneration. Using mass spectrometry, we identified MYH9 as a downstream molecule of P4HB, demonstrating that P4HB affects myoblast migration and thus impacts muscle regeneration. Our results suggest that the accumulation of P4HB in cachectic muscle contributes to regeneration impairment, indicating that P4HB is a potential therapeutic target for cachexia treatment.
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