P.19.4 PDGF-BB is expressed by muscle fibers in myopathies and regulates growth and migration of satellite cells and pericytes

Abstract

PDGF-AA and BB belong to the family of Platelet Derived Growth factors (PDGFs). They activate two different receptors: PDGF-RcfN and PDGF-RcfOfnrespectivelyf∣fnPDGF-AA has been recently involved in the process of fibrosis in muscle dystrophies. In contrast, PDGF-BB could be important in myoblast activation and differentiation. Its role in pathological conditions has not been investigated. Our objective is to study the expression and function of PDGF-BB in human skeletal muscle both in normal and pathological conditions. We studied PDGF-BB and PDGF-Rcβ expression on muscle biopsies from controls and patients with different muscle dystrophies and also in vitro in myoblasts, pericytes and myotubes using immunohistochemistry, WB and ELISA. To study the effect of PDGF-BB on myoblasts and pericytes we performed growth curves, differentiation studies and transwells assays. PDGF-BB is normally expressed in vessels but not in muscle fibers. Muscle fiber expression of PDGF paralleled the degree of muscle degeneration/regeneration in myopathies. In vitro experiments demonstrated that myoblasts and pericytes expressed PDGF-RcfO in the membrane, but did not produce PDGF-BB. In contrast, myotubes did express low levels of PDGF-BB, that increased after injury with ionomycine, SDS or a mechanical damage using glass beads. Moreover, we also observed that myotubes from dystrophinopathy patients expressed higher levels of PDGF-BB than myotubes from controls, facioscapulohumeral muscular dystrophy or dysferlinopathy patients. Finally, PDGF-BB promoted an increase in the growth ratio of myoblasts and pericytes and increased cell migration in the transwell-assays. Our results indicate that PDGF-BB is expressed in muscle fibers during degeneration/regeneration. Further, PDGF-BB may have an important role in growth, activation and migration of muscle stem cells with myogenic potential.