AUF1 Linked to Stem Cell Function and Muscle Regeneration
The stem cells responsible for muscle growth and regeneration are perhaps the best studied of such populations. It seems that most of the new and interesting insights into the nuts and bolts of stem cell biology are coming from this part of the field, in any case. The therapies emerging from research along these lines should include ways to restore the diminished activity of stem cells in older people, with effects most likely similar to present stem cell therapies, but with greater control and selectivity in outcomes. In particular, researchers are very interesting in finding ways to boost muscle growth in older people in order to compensate for the characteristic loss of muscle mass and strength that occurs with aging.
Researchers found that levels of a single protein known as AUF1 determine whether pools of stem cells retain the ability to regenerate muscle after injury and as mice age. Changes in the action of AUF1 have also been linked by past studies to human muscle diseases. More than 30 genetic diseases, collectively known as myopathies, feature defects in this regeneration process and cause muscles to weaken or waste away. Clinical presentation and age of diagnosis vary, but "this work places the origin of certain muscle diseases squarely within muscle stem cells, and shows that AUF1 is a vital controller of adult muscle stem cell fate."
The study results revolve around one part of gene expression, in which the instructions encoded in DNA chains for the building of proteins are carried by intermediates known as messenger RNAs (mRNAs). Proteins comprise the body's structures, enzymes and signals. The expression of certain genes that need to be turned on and off quickly is controlled in part by the targeted destruction of their mRNA intermediates, a job assigned to proteins like AUF1. The investigators found that among the functions controlled by mRNA stability is the fate of stem cells. Following skeletal muscle injury, muscle stem cells receive a signal to multiply and repair damaged tissue, a process that the researchers found is controlled by AUF1. Among the mRNA targets of AUF1 in muscle stem cells, they discovered one that encodes a "master regulator" of adult muscle regeneration, a protein known as MMP9. This enzyme breaks down other proteins, ultimately controlling their expression levels.
The investigators showed that they could restore normal muscle stem cell function and related muscle regeneration in mice lacking AUF1 by repurposing a drug developed for cancer treatment that blocks MMP9 activity. "This provides a potential path to clinical treatments that accelerate muscle regeneration following traumatic injury, or in patients with certain types of adult onset muscular dystrophy. We may be able to treat a variety of degenerative diseases by enhancing resident tissue stem cells through targeting MMP9 and its pathways, even those with normal AUF1."
Link: http://www.eurekalert.org/pub_releases/2016-07/nlmc-gcr072016.php