Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease caused by the absence of dystrophin, a cytoskeleton protein which connects actin to the extracellular matrix. There is a progressive muscular degeneration which eventually leads to early death by respiratory and/or cardiac failure. The mdx mouse, an animal model of DMD, presents sarcolemmal instability, increase of serum creatine kinase and cycles of muscular degeneration/ regeneration. The mild dystrophic phenotype is intensified by physical activity. Galectin 1 is a lectin with affinity by -galactosides and participates in several processes like cellular adhesion, proliferation, apoptosis, tumorigenesis, phagocytosis, inflammatory response, immune reactions, differentiation and muscular regeneration. In proliferating myoblasts, galectin 1 presents low expression and cytoplasmic localization. During fusion and differentiation in myotubes, the expression increases and the protein is secreted. Since galectin 1 is involved in muscular regeneration, this project aims to carry out a comparative analysis of its expression and localization in muscles of mdx and normal mice submitted to physical activity. Four-week-old mice (mdx and normal) will be analyzed in the beginning and in the end of 5 weeks of activity. The evaluation of galectin 1 levels will be done in gastrocnemius and diaphragm muscles by semiquantitative RT-PCR and western blot. The cellular localization will be analyzed by immunohistochemistry. It will be evaluated the degree of muscular degeneration (using Evans blue) and regeneration (number of fibers with central nucleus). The interest in studying galectin-1 in DMD can be justified by two main evidences: increased expression in regenerating muscles and its role in the conversion of dermal fibroblasts into myoblasts, which suggests the viability of galectin-1 therapeutic application.
News published in Agência FAPESP Newsletter about the scholarship: