Résumé :
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Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease due to a deficiency in dystrophin, a 427kDa protein located at the sarcolemma and acting as a linker between cytoskeleton and extracellular matrix Several observations suggest that an increase in intracellular calcium concentration could be involved in the aetiology of muscle fibre injury in DMD. Particularly, previous studies showed that store-operated calcium (SOC) entries can be activated in muscle fibres and that the activity of store-operated calcium channels (SOCCs) was increased in fibres from dystrophic mice. Normal and dystrophic blood-derived CD133+ cells showed an unexpected expression of the B-cell marker CD20, a protein that can play a direct role in the SOC influx and in the modulation of intracellular calcium release through signalling pathways activation. Measurements of intracellular Ca2+ ([Ca2+]i) performed on normal and dystrophic blood-derived CD133+ cells revealed an higher calcium concentration in DMD than normal cells, thus opening the prospective of a calcium impairment possibly involving CD20 activity. Since no natural agonist for CD20 has been identified until now, we considered the possibility that CD20 channel or signal transduction activity can be indirectly modulated by cytokines or growth factors after activation of signalling cascades. By means of ELISA we checked for growth factors and cytokines released by normal and DMD blood-derived CD133+ cells. Supernates from CD133+ stem cells isolated from DMD blood showed an high concentration of brain derived neurotrophic factor (BDNF). Here we showed that a CD20-related signalling pathway able to induce an increase in [Ca2+]i is activated after BDNF stimulation of blood-derived CD133+ cells, supporting the assumption of a "CD20-related calcium impairment" affecting circulating DMD CD133+ cells. Presented findings represent the starting point toward the expansion of knowledge about molecules and pathways involved in the pathology of DMD and in the behavoiur of dystrophic blood-derived CD133+ cells.
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