Everybody ages. Even if people’s life expectancy has significantly increased in the modern day, we still deal with the health problems that our bodies inevitably encounter as we age. For instance, the loss of muscular mass and function, results in atrophy and weakening. In a super-aging country like Japan, where people live longer, this is a serious worry because a lack of adequate muscle strength can significantly lower the quality of life.
A team of researchers from Kyushu University has created a novel antibody that targets and inhibits the malfunction of the protein hepatocyte growth factor, or HGF, which is essential for developing, regenerating, and repairing skeletal muscle. These findings could eventually result in targeted therapies that treat age-related muscle atrophy.
Their findings were published in the journal Aging Cell.
Satellite cells are a type of stem cell population that facilitates muscle growth and regeneration. These satellite cells are triggered to produce new muscle fibers when you exercise or sustain an injury. HGF is one of the main activators that instruct satellite cells to produce new muscle.
Earlier this year, our team found out that HGF undergoes a process called nitration. This is when a molecule of nitrogen dioxide attaches to the amino acid tyrosine on the protein,
This is a common modification we see in biology. However, we found that HGF loses its physiological activity when it becomes nitrated, and this phenomenon accumulates with age.
Ryuichi Tatsumi
In light of this, Tatsumi and his group sought to figure out how to stop the HGF protein from nitrating. Creating antibodies that attach to the protein and prevent it from ever getting nitrated is one of the best methods to achieve this.
To be specific, nitration happens on the 198th and 250th tyrosine amino acid on HGF. So, using rat cell cultures, we developed and screened a series of antibodies that would specifically bind to these areas and block nitration,
After a series of tests, we found two candidate antibodies: 1H41C10 and 1H42F4N. Antibody 1H42F4N blocked nitration of the 198th tyrosine. Surprisingly, 1H41C10 blocked both tyrosine sites.
Ryuichi Tatsumi
The team’s additional research revealed that the new antibodies did not interfere with HGF activity, which allowed satellite cells to continue to be activated.
The team is enthusiastic about their new discoveries and the enormous potential they hold for creating novel therapies for age-related muscle atrophy and other illnesses associated with compromised muscle regeneration.
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Of course, further work is needed before we see a use case in humans, but we are encouraged by the great potential our work has uncovered,
HGF has numerous important functions in a variety of tissues and organs throughout the body. With further researcher we may be able to find other therapeutic applications of HGF in other pathologies.
Ryuichi Tatsumi
Source: Kyushu University – Research Results
Journal Reference: Tanaka, Sakiho, et al. “In Vitro Immuno-prevention of Nitration/Dysfunction of Myogenic Stem Cell Activator HGF, towards Developing a Strategy for Age-related Muscle Atrophy.” Aging Cell, vol. 23, no. 10, 2024, p. e14337, https://doi.org/10.1111/acel.14337.
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