Summary
Plasmin is a potent extracellular protease specialized in the degradation of fibrin
(fibrinolysis). Active plasmin is generated by proteolytic activation of the zymogen
plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen
activator (tPA). α-Enolase constitutes a receptor for plasminogen on several leukocyte
cell types, serving to localize and promote plasminogen activation pericellularly.
However, a role for α-enolase-type plasminogen receptor (PlgR) in myogenesis has never
been demonstrated. In this study, we show that C2C12 mouse myoblasts express PlgR,
being its expression greatly induced during the differentiation process. A monoclonal
antibody against PIgR MAb 11G1, with cell surface-generated plasmin inhibitory abilities,
was able to fully abrogate C2C12 myoblast fusion and differentiation in vitro. Moreover, both plasmin activity and PlgR expression were significantly induced in
regenerating skeletal muscle in vivo, either in experimentally-injured muscle or in the dystrophic muscle of mdx mouse
(an animal model of human Duchenne muscular dystrophy, DMD). The mdx muscle presents
better regeneration capacities and less fibrosis than the human DMD muscle; therefore,
the increase in PlgR/plasmin activity in mdx muscle suggests an important contribution
of the fibrinolytic system in mdx regeneration. This study constitutes the first indication
of α-enolase-type plasminogen receptor as an important component of skeletal myogenesis,
by concentrating and enhancing plasmin generation on the cell surface.
Keywords
α-Enolase-type plasminogen receptor - myogenesis - muscle regeneration - mdx mice
- Duchenne muscular dystrophy