Scientists identify regenerative checkpoint that limits muscle repair

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"Researchers ... have identified a molecular mechanism that constrains skeletal muscle regeneration and myofiber repair, a finding that could lead to improved treatment for conditions like muscular dystrophy and severe injury.

To repair muscle, muscle cells, or myocytes, fuse to one another. But the molecular pathways that signal this cell-to-cell fusion have remained poorly defined. ...

The team ... found that platelet-derived growth factor receptor beta (PDGFRb), a receptor protein located in cell membranes, is a key modulator of myocyte function in adult muscle cells. ...

Through in vitro and in vivo experiments, they found that genetic deletion of PDGFRb enhanced muscle regeneration and increased myofiber size, whereas PDGFRb activation impaired muscle repair. ..."

From the abstract:

"Muscle cell fusion is critical for the formation and maintenance of multinucleated myotubes during skeletal muscle development and regeneration. However, the molecular mechanisms directing cell-cell fusion are not fully understood.

Here, we identified platelet-derived growth factor receptor β (PDGFRβ) signaling as a key modulator of myocyte function in adult muscle cells.

Our findings demonstrated that genetic deletion of Pdgfrb enhanced muscle regeneration and increased myofiber size, whereas Pdgfrb activation impaired muscle repair.

Inhibition of PDGFRβ activity promoted myonuclear accretion in both mouse and human myotubes, whereas PDGFRβ activation stalled myotube development by preventing cell spreading to limit fusion potential.

Furthermore, PDGFRβ activity cooperated with TGF-β signaling to regulate myocyte size and fusion. Mechanistically, PDGFRβ signaling required STAT1 activation, and blocking STAT1 phosphorylation enhanced myofiber repair and size during regeneration. Collectively, PDGFRβ signaling acts as a regenerative checkpoint and represents a potential clinical target to improve skeletal muscle repair."

Scientists identify regenerative checkpoint that limits muscle repair | Cornell Chronicle

PDGFRβ signaling restrains myocyte function to limit the regenerative capacity of skeletal muscle (open access)

Fig. 1 PDGFRβ is induced and activated in stimulated muscle progenitor cells.