Target to repair injured muscles discovered

The team, led by Ashok Kumar, Else and Philip Hargrove Endowed Professor of Drug Discovery and director of the Institute of Muscle Biology and Cachexia, discovered a potential therapeutic target in muscular disorders by identifying a previously unrecognized role of a protein called Fn14 in regulating satellite cell stability and function. They have published their findings in JCI Insight.

Also known as muscle stem cells, satellite cells are responsible for muscle growth, repair and regeneration.

"Our research highlights how Fn14 helps in preserving muscle stem cells and ensuring efficient muscle regeneration," said Meiricris Tomaz da Silva, a post-doctoral fellow in Kumar's lab and the paper's first author. "By better understanding this mechanism, we can explore new ways to support muscle repair in conditions such as Duchenne muscular dystrophy and age-related muscle loss."

Doctoral student Aniket S. Joshi was also on the team.

The study demonstrated that the levels of Fn14 were increased in satellite cells after muscle injury. Conversely, reduction in satellite cell content and function is a significant contributor for skeletal muscle wasting in many conditions, including aging and degenerative muscle disorders, such as muscular dystrophy.

"We have discovered the role of fibroblast growth factor-inducible 14 (Fn14) in the regulation of skeletal muscle regeneration in response to acute injury and in a model of Duchenne muscular dystrophy," reports Kumar. "The study shows that Fn14 is important for maintaining muscle stem cell pool in adult skeletal muscle."

The results of Kumar's present and previous studies published in Life Science Alliance journal demonstrate that Fn14 signaling is crucial for muscle progenitor cells, which are early-stage cells that help form new muscle, to multiply and fuse with injured muscle fibers, promoting repair and regeneration.

"Our findings suggest that augmenting the levels of Fn14 in satellite cells could be an important therapeutic approach for various muscle wasting conditions, such as aging and degenerative muscle disorders," said Kumar.

"These findings deepen our understanding of muscle stem cells and could inform future strategies to enhance muscle regeneration in conditions involving chronic muscle loss."