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

Area of Science:

• Cell Biology
• Molecular Biology
• Physiology

Background:

• Muscle atrophy, including sarcopenia and glucocorticoid-induced myopathy, presents significant public health challenges.
• Preventing muscle atrophy is vital for improving quality of life and longevity.

Purpose of the Study:

• To investigate the effects of recombinant human KAI1 (rhKAI1) on myogenic differentiation.
• To evaluate the protective potential of rhKAI1 against dexamethasone-induced muscle atrophy.

Main Methods:

• Assessed rhKAI1's impact on myogenic differentiation in C2C12 myoblasts and human endometrial stromal cells.
• Utilized a dexamethasone-induced muscle atrophy mouse model.
• Analyzed molecular markers including myogenic regulatory factors, MyHC, atrogin-1, Akt, and AMPK phosphorylation, and fiber-type gene expression.

Main Results:

• rhKAI1 enhanced myogenic differentiation, evidenced by increased myogenic regulatory factors and myotube formation.
• rhKAI1 treatment in a dexamethasone-induced atrophy model increased myotube diameter, restored MyHC expression, and reduced atrogin-1.
• rhKAI1 improved functional deficits in mice, increasing grip strength and rotarod performance, while modulating fiber-type gene expression.

Conclusions:

• rhKAI1 promotes myogenic differentiation and mitigates key features of glucocorticoid-induced muscle atrophy.
• rhKAI1 demonstrates potential as a therapeutic candidate for steroid-induced muscle dysfunction.