In a new study that could pave the way for targeted treatments for various muscle disorders, recent research highlights the crucial mechanisms involved in skeletal muscle regeneration and muscle growth post resistance exercise.
Recent research conducted at the University of Houston College of Pharmacy delves into the key mechanisms governing skeletal muscle regeneration and muscle growth following resistance exercise. This discovery has the potential to lead to the development of specialized therapies for muscle disorders like Muscular Dystrophy, which impact millions of individuals globally.
When it comes to muscles and muscle disorders, the significance of such a breakthrough cannot be overstated.
The Power of Muscles
The fundamental functions of life, such as breathing, regulating whole-body metabolism, and all movements, are controlled by skeletal muscles, including:
-
Walking
-
Running
-
Sitting
-
Standing
-
Smiling
-
And even blinking
In Perspective
Skeletal muscles form during embryonic development through the fusion of specialized cells known as myoblasts. Adult skeletal muscles retain regenerative capacity, attributed to the presence of muscle stem cells called satellite cells.
After an injury, satellite cells go through multiple rounds of cell division followed by differentiation into myoblasts. These myoblasts subsequently fuse with each other and with damaged myofibers to facilitate muscle regeneration.
In various muscle disorders, this intrinsic regenerative capacity of muscles diminishes, leading to muscle mass and function loss.
The Scientific Insight
The researchers at UH discovered that Inositol-requiring enzyme 1, a crucial signaling protein, plays a vital role in myoblast fusion during muscle formation and growth.
“During muscle regeneration, IRE1 enhances the activity of X-box binding protein 1, which in turn stimulates the gene expression of multiple transmembrane proteins necessary for myoblast fusion,” as reported by Ashok Kumar, Else and Philip Hargrove Endowed Professor of pharmacy in the Department of Pharmacological and Pharmaceutical Sciences at the UH College of Pharmacy, in EMBO Reports.
According to the researchers, increasing the levels of IRE1 or XBP1 in muscle stem cells externally, followed by their injection into patients’ muscle tissues, can enhance muscle repair and reduce disease severity.
“We also found that elevating the levels of IRE1α or XBP1 in myoblasts leads to the formation of myotubes (muscle cells) with an increased diameter,” stated Kumar.
This increase in diameter can have a significant impact.
“Size is crucial for muscles. Muscles only grow in size, not in number,” cited Aniket Joshi, a graduate student in Kumar’s lab and first author of the article. “Individuals with more muscle mass have larger muscle cells. Larger muscles typically perform better—capable of lifting more weight, running and walking faster, improving overall body metabolism, and aiding in the prevention of various diseases such as type II diabetes.”
Showcasing their Discoveries
This recent research represents another notable achievement for Kumar’s team. In 2021, their research published in the ELife journal elucidated the role of the IRE1α/XBP1 signaling axis in the regeneration of healthy skeletal muscle post-acute injury and in Duchenne Muscular Dystrophy models. In this study, they highlighted the essential cell-autonomous role of the IRE1α/XBP1 signaling axis in satellite cells as well.
In addition to Kumar and Joshi, post-doctoral fellow Meiricris Tomaz da Silva and research assistant professor Anirban Roy contributed to the research in Kumar’s lab. Other authors from the University of Houston on the article include Micah Castillo, Preethi Gunaratne, Mingfu Wu, Yu Liu, and former post-doctoral fellow in Kumar’s lab Tatiana E. Koike, alongside Takao Iwawaki from Kanazawa Medical University, Japan.
