Scientists from Tokyo Metropolitan University have discovered that a protein called platelet-derived growth factor subunit B (PDGF-B) is continuously secreted by skeletal muscle cells and helps repair muscles by encouraging proliferation of myoblasts (muscle stem cells). Unexpectedly, they discovered that PDGF-B also helps muscle fiber growth. They confirmed that this corresponded to fibers contracting more strongly. Their findings promise breakthrough therapies for the treatment of muscle atrophy and injury.
Myokines are small proteins secreted by skeletal muscle cells. They have a wide range of functions and can act on cells near and far from where they are made. A full picture of how myokines affect cellular processes is far from clear, but they are thought to play an important role in exercise-related bodily functions, particularly the maintenance of muscle tissue.
A team led by Associate Professor Yasuko Manabe of Tokyo Metropolitan University investigated how myokines affect muscle cell behavior. Through extensive experiments, they discovered that a myokine known as platelet-derived growth factor subunit B, or PDGF-B, is constitutively secreted by skeletal muscle (i.e. say without any stimulus). To understand its role, they took myoblasts, precursor cells that then differentiate into muscle fibers, and exposed them to PDGF-B. They were able to clearly show that PDGF-B induced greater proliferation of myoblasts.
Curiously, they also found that PDGF-B impacted cells that had already differentiated. They took myotubes, a stage of muscle fiber development, and exposed them to the same myokine. Myotubes treated in this manner exhibited significantly greater maturation, visibly increasing in diameter under microscopic observation. They also expressed more myosin heavy chain, a key component of the protein structure of myosin, the molecular engine responsible for muscle contraction.
Using a recently developed technique based on observing the reaction of myotubes to an electrical impulse, this was shown to correspond directly to increased contractile force. Thus, PDGF-B not only helps to make more muscle, but makes them stronger. But this does not mean that the two processes are randomly accelerated. They noticed subtle differences in PDGF-B signaling pathways between myotubes and myoblasts; the team thinks that these differences may be involved in the transition of cells from a proliferation phase to a maturation phase.
The article is published in the journal Communications on biochemical and biophysical research.
The team’s work clearly shows that PDGF-B is involved in muscle regeneration and is a big step forward in developing effective treatments for muscle damage and atrophy as well as therapeutic regimens to improve muscle performance.
Hiroki Hamaguchi et al, PDGF-B secreted by skeletal muscle enhances myoblast proliferation and myotube maturation via activation of the PDGFR signaling cascade, Communications on biochemical and biophysical research (2022). DOI: 10.1016/j.bbrc.2022.11.085
Provided by Tokyo Metropolitan University
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