Recombinant Human KAI1/CD82 Attenuates Glucocorticoid-Induced Muscle Atrophy by Promoting Myogenic Differentiation

TL;DR

This study shows that recombinant human KAI1 helps prevent muscle atrophy caused by steroids by promoting muscle cell development and improving muscle function.

Contribution

The study introduces rhKAI1 as a novel candidate for preventing glucocorticoid-induced muscle atrophy.

Findings

rhKAI1 promotes myogenic differentiation and increases myotube formation in both mouse and human cells.

rhKAI1 reduces dexamethasone-induced muscle atrophy by modulating Akt and AMPK phosphorylation.

rhKAI1 improves muscle function and fiber-type gene expression in a mouse model of glucocorticoid-induced atrophy.

Abstract

Sarcopenia and glucocorticoid-induced myopathy are significant forms of muscle atrophy that pose considerable public health challenges. In this regard, preventing muscle atrophy is crucial for enhancing quality of life and increasing life expectancy. In this study, we investigated the effect of recombinant human KAI1 (rhKAI1) on myogenic differentiation and its protective effect against dexamethasone-induced muscle atrophy. rhKAI1 enhanced myogenic differentiation in both murine C2C12 myoblasts and primary human endometrial stromal cells, as evidenced by upregulation of myogenic regulatory factors and increased myotube formation. These effects were accompanied by increased phosphorylation of Akt and AMPK. In a dexamethasone (Dex)-induced atrophy model, rhKAI1 increased myotube diameter, restored MyHC expression, and reduced the expression of the E3 ligase atrogin-1, accompanied by increased phosphorylation of Akt and AMPK. In addition, rhKAI1 administration improved Dex-induced functional impairment in mice, as reflected by increased grip strength and improved rotarod performance. Molecular analyses further showed that rhKAI1 modulated Dex-induced fiber-type-related gene expression by restoring MYH7 (type I) and reducing MYH4 (type IIb) expression. Collectively, our findings demonstrate that rhKAI1 promotes myogenic differentiation and alleviates several functional and molecular features associated with glucocorticoid-induced muscle deterioration. These results support the potential of rhKAI1 as a candidate molecule for further investigation in steroid-induced muscle dysfunction.

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