The Loss of HJV Aggravates Muscle Atrophy by Promoting the Activation of the TβRII/Smad3 Pathway

Area of Science:

• Muscle physiology and pathophysiology
• Iron regulation
• Cell signaling pathways

Background:

• Hemojuvelin (HJV) is a protein crucial for iron regulation, with roles in skeletal muscle, heart, and liver.
• The specific function of HJV in muscle health and disease, particularly muscle atrophy, remains largely unclear.

Purpose of the Study:

• To investigate the role of HJV in disuse-induced muscle atrophy.
• To elucidate the underlying molecular mechanisms connecting HJV to muscle wasting.

Main Methods:

• Utilized a mouse model with muscle-specific deletion of HJV (MKO) and wild-type (WT) littermates.
• Employed hindlimb unloading (HU) to induce muscle atrophy.
• Analyzed protein expression of HJV, muscle ubiquitin ligases, transforming growth factor-β type II receptor (TβRII), and phosphorylated Smad3 (p-Smad3).
• Performed TβRII knockdown in MKO mice.

Main Results:

• Hindlimb unloading caused soleus muscle atrophy in WT mice, with decreased HJV expression.
• Muscle-specific HJV deletion exacerbated atrophy and increased muscle ubiquitin ligase expression post-HU.
• HU elevated TβRII and p-Smad3 levels, effects more pronounced in MKO mice.
• TβRII knockdown in MKO mice ameliorated atrophy and normalized TβRII/Smad3 pathway activation.

Conclusions:

• Absence of HJV promotes myofiber atrophy during disuse by activating the TβRII/Smad3 signaling pathway.
• HJV plays a protective role against disuse-induced muscle atrophy.
• HJV represents a potential therapeutic target for combating muscle atrophy.