Fortunately, skeletal muscles have a high potential for regeneration, unlike other organs. When injured, muscle stem cells, known as satellite cells and located between the individual muscle fibers, rapidly begin to proliferate and subsequently replace the damaged muscles cells. New research from researchers from the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany, have shown that a protein called Prmt5 plays a key role in regulating the activity of muscle satellite cells. These data gave rise to new studies that would like to examine the impact of Prmt5 in muscle disorders.
Satellite cells in skeletal muscles are small, spherical stem cells in between the individual muscles fibers. Normally, these cells remain almost completely inactive, but when a muscle is immediately begin to proliferate and heal the injury by replacing damaged muscles fibers.
When satellite cells react to an injury, they undergo a transition from their inactive state to one of increased activity. This transition must be finely balanced because uncontrolled proliferation of satellite cells in healthy muscle tissue increases the risk of tumor formation. Conversely, muscle regeneration is impeded if the satellite cells are not activated fast enough when muscles are injured.
Now a research team headed by Thomas Braun from the Max Planck Institute for Heart and Lung Research in Bad Nauheim has now identified a gene that plays a decisive role in regulating the activity of satellite cells. Braun and his colleagues isolated muscle satellite cells from laboratory mice and identified 120 genes that are instrumental for the function of these cells.
Next, they switched off one of these genes, Prmt5, in the satellite cells of adult mice. “In healthy mice, switching off Prmt5 in the satellite cells had no effect on the muscles. But when the mice had a muscle injury, the results were completely different”, says Ting Zhang, the study’s lead author. No signs of regeneration were observed in Prmt5-deficient mice, but the muscles of control mice that had an active Prmt5 gene healed normally. “Instead of growing new muscle tissue, the mice without Prmt5 eventually developed clear signs of fibrosis”.
Braun and others further examined how Prmt5 regulates muscle regeneration. In mice without Prmt5, the number of satellite cells was noticeably reduced. Prmt5 seems to regulate proliferation activity of satellite cells. Furthermore, these results indicated that Prmt5 also prevents satellite cells from dying prematurely and plays a key role in transforming them into functional muscle fibers.
Braun and his colleagues hope their study will help them gain a better understanding of muscle disorders in humans. “The loss of muscle tissue in the absence of Prmt5 shows clear parallels to degenerative muscle disorders such as Duchenne muscular dystrophy”, says Johnny Kim, a member of Braun’s working group. In fact, the Bad Nauheim team now hopes that in the future, mice lacking the Prmt5 gene can serve as models for this particular disorder. “But we also want to study the etiological effects of Prmt5 regarding the genesis of muscular hypertrophies and certain tumor types,” Kim adds.