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bioRxiv · 10.1101/2025.10.02.679938

Age-dependent Dysferlin Accumulation in Macrophages Promotes STAT1 Activation via Calcium Influx, Impairing Myogenesis

Tominaga, K.·Tominaga, N.
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Abstract

DYSF functions as a regulator of Ca{superscript 2} in the skeletal muscle and facilitates muscle repair following injury. It is also highly expressed in monocytes and macrophages and related to inflammation, immune regulation, and the mononuclear phagocyte system. Macrophages are pivotal in driving myogenesis, and specific cytokine-induced macrophage differentiation plays a role in maintaining skeletal muscle during disease and aging. Thus, a comprehensive understanding of the mechanisms by which DYSF operates in macrophages may inform the development of novel treatments for muscle atrophy. In this study, we demonstrated that DYSF expression is associated with monocyte differentiation and increases with age. Our findings indicate that DYSF overexpression induces the generation of M1-type macrophages, which subsequently secrete inflammatory cytokines and promote cell invasion. Furthermore, we observed that DYSF regulates Ca{superscript 2} influx into the cell and activates the STAT1 signaling pathway, whereas DYSF deficiency suppresses these processes. Macrophages overexpressing DYSF are associated with the inhibition of myoblast differentiation during myogenesis in a co-culture system involving macrophages and myoblasts. Therefore, the balance between the STAT1 signaling pathway and Ca{superscript 2}, which are regulated by DYSF abundance, may play a crucial role in myogenesis.

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Tominaga, K., Tominaga, N.. 2025-10-04. Age-dependent Dysferlin Accumulation in Macrophages Promotes STAT1 Activation via Calcium Influx, Impairing Myogenesis. https://doi.org/10.1101/2025.10.02.679938

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