Well known for its role in inflammation and already targeted by several anti‑inflammatory drugs, prostaglandin E₂ (PGE₂) may also play a key role in muscle repair. At the Centre de recherche Azrieli du CHU Sainte‑Justine, the team led by researcher Nicolas Dumont, with a key contribution from Thomas Molina (then a PhD student), has identified a central pro‑inflammatory mechanism capable of limiting muscle fibrosis—a process involved in several diseases, including Duchenne muscular dystrophy.
Published last Friday in Cell Death & Differentiation, the study shows that PGE₂ plays a decisive role in muscle tissue repair, notably by helping maintain a balance between fibrosis—the scar tissue that forms after injury—and muscle regeneration.
“Some components of inflammation are essential for proper tissue repair,” explains Nicolas Dumont, also a professor at Université de Montréal and holder of the Canada Research Chair in Stem Cells and Neuromuscular Diseases. “PGE₂ is a good example: it plays a beneficial role by controlling cells that could otherwise become problematic.”
Useful cells—whose activity must be tightly regulated
To understand how PGE₂ acts, the team examined the cells it affects, particularly a lesser-known type: fibroadipogenic progenitors (FAPs), which contribute to muscle repair.
Their activity must be finely regulated. When they accumulate or become overly active, they produce excessive fibrosis.
These cells are also the main source of PGE₂ in muscle. They produce it to limit their own proliferation and promote their disappearance at the right time. In this way, PGE₂ acts as a natural brake, preventing excessive buildup of fibrous tissue.
“What is fascinating is that the same molecule can have different effects depending on the cell type: it supports the activity of cells responsible for muscle regeneration while restraining those that contribute to fibrosis,” notes Thomas Molina.
When the balance is disrupted
This central role of PGE₂ becomes especially clear when its production is impaired—even in the presence of inflammation. This is the case in Duchenne muscular dystrophy, a severe degenerative disease affecting approximately 1 in 4,000 boys and characterized by progressive and irreversible muscle weakness.
As a result, FAPs are no longer properly controlled, accumulate, and produce more fibrosis, contributing to the gradual decline in muscle function.
Promising avenues
These findings suggest that, for certain muscle diseases, rather than blocking inflammation, it may be more effective to modulate specific key signals such as PGE₂, in order to enhance their beneficial effects at the right time.
By highlighting the unexpected role of a well-known molecule, this study reminds us that muscle repair depends on subtle balances, with PGE₂ emerging as a central regulator.