Caracterização do perfil de expressão da molécula orientadora por repulsão a (RGMA) na musculatura esquelética atrofiada por denervação

Abstract

Several physiological stimuli are capable of inducing modifications in the skeletal muscle, leading to an increase or loss of muscle mass. Many molecules are involved in both processes and recent studies have revealed the presence of the Repulsive Guidance Molecule a (RGMa) in the sarcolemma and sarcoplasm of skeletal muscle cells, relating it to the muscle hypertrophy pathway. However, little is known about the muscle atrophy process and understanding its mechanisms allows the development of gene therapies. The present work proposed to investigate a possible association of RGMa with the muscle fiber size regulation through the muscle atrophy by denervation model. It was possible to observe an increase in RGMa mRNA expression, as well as of the soluble form of the molecule after sciatic nerve axotomy, suggesting activation of a compensatory hypertrophic mechanism. The expression of the ancored form is downregulated. The expression of the molecule is restricted to only a few atrophic muscle fibers, in a similar pattern from that found for normal muscle fibers. The signaling pathway induced by the soluble form of RGMaBMP4/Smad1/5/8-RohA appears to be activated during denervation, probably to induce muscle hipertrophy to control muscle loss. Our findings reinforce that RGMa may indeed be associated with the muscle hypertrophy pathway.