Résumé :
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Muscular dystrophies are a heterogeneous group of muscle degenerating diseases for which no effective treatment exist. A potential treatment strategy could be developed by studying DLK1 and myostatin regulation. DKL1 and myostatin are known to generate muscle hypertrophy phenotypes and therefore these may be potential targets for intervention or be used in gene therapeutic strategies of muscular disorders. DLK1 is involved in embryonic muscle development and it has been shown to induce muscle hypertrophy in transgenic mice and callipyge sheep. Myostatin negatively regulates myogenesis, and inactivation leads to heavy muscle growth. The expression of DLK1 and myostatin was studied in a set of experiments. In transgenic mice over expressing DLK1 it was found that myostatin mRNA levels were significantly lower compared to the controls. The effect on proliferation and differentiation were tested in vitro by transfecting C2C12 cells with full length mouse Dlk1. DLK1 did not affect the myogenic potential of the cells; but it appeared to keep the cells in a proliferative state for a longer time before initiation of differentiation. Like in the regeneration studies, myostatin mRNA was down regulated in DLK1-C2C12 cells. In addition we found decorin upregulated. Furthermore, the expression of DLK1 and myostatin was studied in human satellite cell cultures. A high level of DLK1 was observed in nonproliferating G0 cells but during proliferation and differentiation the level of DLK1 was highly down regulated. The expression of myostatin was down regulated in G0 and proliferating human satellite cell cultures, but was highly up regulated in differentiating cultures. Thus, the results again indicate that DLK1 interact with the expression of myostatin. The studies were made using Taqman® RT-qPCR and immunohistochemistry.
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