Recent research published in EMBO Reports led by a team from the University of Houston College of Pharmacy has identified key mechanisms of skeletal muscle regeneration and growth of muscles following resistance training exercises. This breakthrough may open new avenues for the development of targeted therapies for various muscle disorders such as Muscular Dystrophy which affects millions of people around the World.
Muscles may be more important than you realize
The importance of this discovery cannot be overstated when it comes to muscles and muscle disorders. It is so very important because muscles are the very core of life, even something that we don’t really think about often such as breathing is controlled by skeletal muscles, and so is the regulation of whole-body metabolism. Every single movement that you make from blinking to walking, to sitting and standing, even simply smiling is controlled by skeletal muscles.
Skeletal muscles are formed during embryonic development by the fusion of myoblast cells. Adult skeletal muscles maintain regenerative capacity which is attributed to the presence of muscle stem cells (satellite cells).
Satellite cells undergo proliferation rounds after injury followed by differentiation into myoblasts, which once more fuse with each other as well as with other injured myofibers to achieve muscle regeneration. However, in muscular disorders, the capacity to regenerate like this is diminished which results in the loss of muscle mass and function.
What they discovered
“During muscle regeneration, IRE1 augments the activity of X-box binding protein 1 which in turn stimulates the gene expression of multiple transmembrane proteins required for myoblast fusion,” reports Ashok Kumar, Else and Philip Hargrove Endowed Professor of pharmacy in the Department of Pharmacological and Pharmaceutical Sciences at the UH College of Pharmacy.
The researchers suggest that Inositol-requiring enzyme 1, a key signaling protein, is essential for myoblast fusion during muscle formation and growth and increasing the levels of IRE1 or XBP1 in muscle stem cells outside the body, followed by their injection in patients’ muscle tissues will improve muscle repair and reduce the severity of the disease.
“We also found that augmenting the levels of IRE1α or XBP1 in myoblasts leads to the formation of myotubes (muscle cells) having an increased diameter,” said Kumar.
“Size is very important for muscle. Muscle grows only in size, not in number,” said Aniket Joshi, a graduate student in Kumar’s lab and first author on the article. “Muscular people have larger muscle cells. Larger muscles generally work better- can lift more weight, run and walk faster, and improve overall metabolism of the body and prevent various diseases, such as type II diabetes.”
Previous research
This research is not the first muscle flex for this team, previously Kumar’s lab published in the ELife journal describing the role of the IRE1α/XBP1 signaling axis in the regeneration of healthy skeletal muscle after acute injury and in models of Duchenne Muscular Dystrophy. In this study, they found that the IRE1α/XBP1 signaling axis also plays an important cell-autonomous role in satellite cells.
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References/Sources/Materials provided by:
https://stories.uh.edu/2024-skeletal-muscle-regeneration/index.html