Possible Involvement of CSPG4 in Promoting Endothelial Cell Migration and Contributing to Angiogenesis during Skeletal Muscle Regeneration and Development in the Rat

Skeletal muscle regeneration is a complex process that requires coordinated interactions between myogenic and vascular cells. Chondroitin sulfate proteoglycan 4 (CSPG4), a cell surface proteoglycan, had been shown to be expressed around immature myofibers in patients with Duchenne muscular dystrophy, suggesting its role in muscle regeneration. In the present study, we found that CSPG4 is transiently expressed by regenerating myofibers upon muscle injury in the rat. We generated the CSPG4 knockout (KO) rats to investigate its role in muscle regeneration. In CSPG4 KO rats, skeletal muscle development was perturbed with impaired angiogenesis. When muscle regeneration was induced, CSPG4 KO rats showed a reduced number of CD31-positive cells at the regenerating site. These results suggest the role of CSPG4 in angiogenesis during muscle regeneration and development. In vitro, coculture of CSPG4-expressing mesenchymal progenitor cells (MPC) promoted vascular endothelial cell migration, whereas the KO of CSPG4 in MPC abrogated the upregulation of endothelial cell migration. Our findings identify CSPG4 as a key regulator of vascular endothelial cell recruitment during muscle vascular remodeling and highlight its potential as a therapeutic target for Duchenne muscular dystrophy, which is characterized by impaired angiogenesis.