Plasminogen deficiency exacerbates skeletal muscle loss during mechanical unloading in developing mice

Area of Science:

• Physiology
• Molecular Biology
• Space Biology

Background:

• Mechanical unloading, such as microgravity or hindlimb suspension, induces skeletal muscle atrophy, leading to frailty.
• Understanding the molecular mechanisms of muscle atrophy is crucial for developing countermeasures.
• Fibrinolysis-related proteins, including plasminogen, are elevated in unloaded muscles.

Purpose of the Study:

• To investigate the role of the fibrinolytic system, specifically plasminogen, in mechanical unloading-induced skeletal muscle atrophy.
• To determine whether plasminogen deficiency affects protein degradation pathways like autophagy and the ubiquitin-proteasome system.

Main Methods:

• Proteomic analysis of gastrocnemius (Gast) and soleus muscles from space-flown mice.
• Hindlimb suspension model in wild-type and plasminogen-deficient (Plg-/-) mice.
• Analysis of muscle mass, autophagy markers (beclin1, LC3B), and ubiquitin ligases (atrogin-1, MuRF1).

Main Results:

• Plasminogen deficiency exacerbated muscle mass loss and gastrocnemius atrophy in hindlimb-unloaded mice.
• Plasminogen deficiency increased autophagy markers but did not affect ubiquitin ligase expression in unloaded muscles.
• The Akt/mTOR pathway remained unaffected by plasminogen deficiency or hindlimb unloading.

Conclusions:

• Plasminogen deficiency accelerates protein breakdown via the autophagy-lysosome pathway, not the ubiquitin-proteasome system, in mechanically unloaded muscles.
• Plasminogen and the fibrinolysis system may play protective roles against skeletal muscle atrophy induced by mechanical unloading.