Researchers have discovered that the nuclear receptor REV-ERB is crucial in muscle regeneration.
A team from Saint Louis University have pinpointed the role REV-ERB plays, which could lead to new treatment options for muscle disorders and injuries.
“REV-ERB is an interesting nuclear receptor that helps coordinate our metabolism with our daily routine,” Colin Flaveny, Ph.D., an assistant professor of pharmacology and physiology, said in a statement. “We’re studying the protein to see if turning its activity up or down can influence the way muscle regenerates after injury or illness.”
Skeletal muscle comprises about 40 to 50 percent of the total body mass of humans and is essential for postural support, locomotion and breathing.
Skeletal muscle normally maintains muscle mass and function in response to minor injuries and normal wear and tear without much trouble.
However, the body’s natural muscle regeneration may not be able to keep up, and the loss of skeletal muscle mass and strength is common in cases of traumatic injury or illnesses such as congestive heart failure, chronic obstructive pulmonary disease, severe burns, cancer and HIV infection.
Severe injuries—with more than 20 percent loss of muscle mass—cause normal muscle regeneration to fail to keep pace with the regenerative demands, which can trigger widespread fibrosis and loss of muscle function.
Muscle regeneration eventually may become unable to keep the pace, despite the use of dietary interventions, anabolic steroids or non-steroidal anti-inflammatories, which are often accompanied by severe side effects that may further reduce the quality of life.
“Identifying new means of accelerating muscle regeneration has proved a daunting challenge,” Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, said in a statement. “Therefore understanding the underlying mechanisms that regulate muscle cell regeneration and coordinate regenerative repair could provide future therapeutic options for stymieing the loss of muscle function in the traumatically injured.”
Muscle stem cells produce myoblasts that either reproduce or form muscle tissue. For skeletal muscle to successfully regenerate after a traumatic injury, muscle fiber through elevated myoblast proliferation and differentiation must be replenished.
The researchers found that a decline in the expression of REV-ERB precedes myoblast differentiation, while an increase in REV-ERB expression is involved in the regulation of mitochondrial and metabolic function in fully differentiated skeletal muscle.
The research team discovered that the protein is a regulator of muscle differentiation that can be targeted to stimulate muscle regeneration and may be helpful in treating muscle diseases including muscular dystrophy, sarcopenia and cachexia.
“We demonstrate that REV-ERB can stimulate muscle regeneration upon acute muscle injury in an animal model,” Burris said. “Our findings reveal that REV-ERB may be a potent therapeutic target for the treatment of a myriad of muscular disorders.”