Duchenne Muscular Dystrophy is infected with Piezo1 protein

Duchenne Muscular Dystrophy is infected with Piezo1 protein ...

According to a team at the Perelman School of Medicine of Pennsylvania, one protein, Piezo1, is critical to identifying muscle stem cells'' unique shapes and responses to injury, but it is in limited supply.

Despite the fact that they re-activated Piezo1, muscle stem cells in mice were able to return to their normal, distinct-shaped states, so that they could repair broken down, dystrophic muscles. These findings, published in Science Advances, open the door to possible molecular-level therapies that might slow or even halt the development of muscular dystrophy.

The researchers found that muscle stem cells have a variety of extensions that are used to sense their environment to respond to injury, all of which is controlled by the protein Piezo. This is, contrary to previous belief, which found muscle stem cells to be very round and dormant in unamaged muscles.

The Piezo1 protein was identified a decade ago and won a Nobel Prize last year for those who discovered it, but it''s function in skeletal muscles has been largely unknown. However, when Penn researchers examined it in muscle stem cells, they discovered that it influenced how the cells formed and coordinated their response to muscle damage.

Most muscle stem cells are used by the body to repair muscle tissue damage. Little has been known about how they actually perform that because most research on them has been done through point-in-time surveys in the laboratory. However, Mourkioti and her team were able to examine mice and discovered that their muscle stem cells have protrusions they use to communicate with each other that make them look similar to neurons (nerve cells).

The Mourkiotis team discovered that muscle stem cells are grouped in three groups: responsive (or active) cells, intermediate cells, and sensory cells (which are closer to unassigned stem cells). Amid an injury, the researchers found that muscle stem cells concentrate on a rapid response from their responsive cells. If an injury is big enough or requires enough time, intermediate cells and, eventually, sensory cells are brought in to treat the damage and adjust their form accordingly.

If muscle stem cells were organized like an army, the responsive cells with fewer (or no) protrusions would be the shock troops, and the sensory cells with four or more protrusions would be similar to the front-line troops he might call in if the front-line troops were overwhelmed. These reserve cells shift their form to have fewer protrusions.

Piezo1 proteins would be used as the general in the army. These proteins seemed to have the potential to dictate the structure of the protrusions on each cell.

Duchenne muscular dystrophy is a genetic disorder that is characterized by a persistent breakdown of muscles and therefore, a constant need for repair. When the researchers examined muscle stem cells reactions to injuries in dystrophic mice, they noticed significant improvements in the transition from the sensory state to the active state. Cells also had protrusions that were thicker and longer, indicating that they weren''t being controlled correctly.

Effectively, without an able general leading them, the muscle stem cells army falls into disarray, and its distressed by the amount of response necessary to recover the damage caused by Duchenne muscular dystrophy.

Mourkioti and her team believe that they have discovered the right way to move the tide.

Animals with dystrophic muscles noticed the muscle stem cells returning to their normal structure and function, indicating that muscle regeneration was stronger than previously.

Although progress on treatment for Duchenne muscular dystrophy has been made in the last decade, current strategies do not take muscle stem cells into account, according to Mourkioti. However, if we concentrate on minimize stem cell exhaustion and maintaining the regenerative capability of muscle stem cells, our findings suggest that reactivating Piezo1 might be crucial to that and it may be used alone or in conjunction with other therapies.

This work may have specific implications for Duchenne muscular dystrophy, but it may also benefit other people with weak muscles due to stem cell deficiencies, including natural aging.

Mourkioti and her team hope to investigate whether additional injection therapies may be utilized to maintain muscle stem cell activity. They also want to further investigate Piezo1s functions in the body and perform more experiments in pre-clinical dystrophic animals.

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