CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor

Area of Science:

• Muscle physiology and molecular biology
• Sarcopenia research
• Cytokine signaling in muscle

Background:

• Sarcopenia is characterized by decreased muscle mass and strength.
• Chemokine ligand 5 (CCL5) and its receptor CCR5 are elevated in sarcopenic muscle.
• The role of CCL5 in inducing sarcopenia remains unclear.

Purpose of the Study:

• To investigate if CCL5 and CCR5 induce sarcopenia-like effects in skeletal muscle.
• To elucidate the molecular mechanisms underlying CCL5-induced muscle atrophy.

Main Methods:

• Overexpression of CCL5 in mouse tibialis anterior (TA) muscle via electroporation.
• Treatment of C2C12 myotubes and isolated flexor digitorum brevis (FDB) fibers with recombinant CCL5 (rCCL5).
• Assessment of muscle mass, fiber diameter, protein content, E3-ligase gene expression, and oxidative stress markers.
• Evaluation of CCR5 involvement using the antagonist maraviroc (MVC).

Main Results:

• CCL5 overexpression in TA muscle induced sarcopenia, reducing muscle strength, mass, fiber diameter, and sarcomeric proteins, while upregulating E3-ligases.
• Similar sarcopenic phenotypes were observed in cultured myotubes and FDB fibers treated with rCCL5.
• CCL5 treatment increased reactive oxygen species (ROS) production and carbonylated proteins, indicating oxidative stress.
• CCR5 antagonism with MVC prevented the sarcopenic effects induced by rCCL5.

Conclusions:

• CCL5 acts as a novel myokine that promotes a sarcopenia-like phenotype.
• The sarcopenic effects of CCL5 are mediated through the CCR5 receptor.
• CCL5-induced oxidative stress contributes to muscle atrophy.