Research recently published by the University of Houston College of Pharmacy identifies key mechanisms of skeletal muscle regeneration and growth after resistance exercise. This finding opens the door to the development of therapies targeting a variety of muscle disorders, including muscular dystrophy, which affects millions of people worldwide.
When it comes to muscles and muscle disorders, the importance of a discovery like this cannot be overstated.
The muscle of muscles
The fundamental function of life, breathing, is controlled by skeletal muscles, as is the regulation of the metabolism of the entire body and every movement we make:
In context
Skeletal muscles are formed during embryonic development by the fusion of hundreds of specialized cells called myoblasts. Adult skeletal muscles maintain regenerative capacity, which is attributed to the presence of muscle stem cells, called satellite cells.
Following injury, satellite cells undergo several rounds of proliferation followed by their differentiation into myoblasts. These myoblasts fuse again with each other and with the injured myofibers to achieve muscle regeneration.
In many muscle disorders, this intrinsic ability of muscles to regenerate is impaired, leading to loss of muscle mass and function.
The science
UH researchers discovered that inositol-requiring enzyme 1, a key signaling protein, is essential for myoblast fusion during muscle formation and growth.
“During muscle regeneration, IRE1 increases the activity of X-box binding protein 1, which in turn stimulates gene expression of multiple transmembrane proteins required for myoblast fusion,” reports Ashok Kumar, the Else and Philip Hargrove Professor of Pharmacy in the Department of Pharmacological and Pharmaceutical Sciences in the UH College of Pharmacy, in EMBO Reports.
According to the researchers, increasing the levels of IRE1 or XBP1 in muscle stem cells outside the body, followed by injecting them into patients’ muscle tissues, will improve muscle repair and reduce disease severity.
“We also found that increasing the levels of IRE1α or XBP1 in myoblasts leads to the formation of myotubes (muscle cells) that have a larger diameter,” Kumar said.
This increase in diameter can be significant.
“Size is very important for muscles. Muscles grow only in size, not in quantity,” said Aniket Joshi, a graduate student in Kumar’s lab and first author on the paper. “Muscular people have larger muscle cells. Bigger muscles generally perform better: they can lift more weight, run and walk faster, and improve the body’s overall metabolism and prevent several diseases, such as type II diabetes.”
Flexing his muscles
This new research is not the first from Kumar’s team. In 2021, research from Kumar’s lab published in the journal ELife described 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 autonomous role in satellite cells.
Along with Kumar and Joshi, postdoctoral researcher Meiricris Tomaz da Silva and research assistant professor Anirban Roy conducted the research in Kumar’s lab. Other authors on the paper from the University of Houston include Micah Castillo, Preethi Gunaratne, Mingfu Wu, Yu Liu and a former postdoctoral researcher in Kumar’s lab, Tatiana E. Koike, along with Takao Iwawaki of Kanazawa Medical University, Japan.