Caracterização in vitro e in vivo dos efeitos do tratamento de células musculares com a molécula orientadora por repulsão a (rgma) durante a regeneração muscular

Abstract

The muscular system performs a variety of functions related to locomotion, respiration, body support, hormone synthesis, and repair. The main component involved in muscle repair and development are satellite cells, which are embedded in a complex niche composed of interstitial cells and vascular and neural networks. The Repulsive Guidance Molecule member a (RGMa) was initially described during axonal growth and migration during nervous system development. RGMa also plays roles in non- neural tissue, such as in bone formation, immune response, angiogenesis, and muscle tissue development. Recent work by our research group revealed that RGMa is expressed in skeletal muscle precursor cells and that its overexpression induces hyperplasia and hypertrophy in immortalized skeletal muscle cells. Thus, the present work sought to investigate the relationship between satellite cells and RGMa during muscle regeneration. In the first chapter, we observed that RGMa is capable of promoting hypertrophy when injected into the tibialis anterior muscle, both in the musculature of healthy animals and in a scenario of chemical muscle injury caused by barium chloride. Together, these results reveal possible therapeutic strategies, involving molecular biology, to resolve or alleviate symptoms caused by myopathies. In the second chapter, we characterize the effects of RGMa on satellite cells in vitro. RGMa was found in the nucleus of satellite cells, probably being transported by BMP, as the treatment of these cells with a BMP inhibitor, dorsomorphine, was able to inhibit the nuclear localization of RGMa. Furthermore, RGMa seems to induce the proliferation of satellite cells, as well as their differentiation in an environment with favorable conditions. Our results bring new information related to the heterogeneity and behavior of satellite cells cultured in the presence of RGMa.