Lu dans le livre des résumés des présentations faites lors du congrès "13éme journées de la Société Française de Myologie SFM" tenu à l'Ecole Normale Supérieure de Lyon les 23-24 & 25 Novembre 2015 http://www.congresjsfm.org/?q=fr/node/15
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FUNCTIONAL ALTERATION OF SATELLITE CELLS IN MYASTHENIA GRAVIS: KEY ROLE OF MYOD AND MYOG
Mohamed Attia, Marie Maurer, Jacky Bismuth, Sylvain Bougoin, Gillian Butler-
Browne and Sonia Berrih-Aknin
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617,
Center of Research in Myology, F-75013, Paris, France
Myasthenia gravis (MG) is a neuromuscular disease caused by autoantibodies against Acetylcholine Receptor. MG is characterized by fatigability and fluctuating muscle weakness. Muscle homeostasis and regeneration is carried out by local stem cells called satellite cells (SCs). However, molecular and cellular mechanisms of myogenesis in MG are still unknown.
Muscle biopsies from MG and healthy age-‐matched controls were collected. SCs were isolated using explants culture and positive selection of CD56+ cells. Proliferation and differentiation of myoblasts in vitro were assessed by cell counting and muscle myosin immunolabeling (from day 0 to day 4). Localization of myogenic markers in muscle biopsies of MG patients and healthy controls was determined using immunolabeling. mRNA expression was analysed by real-‐time qPCR.
We show that SCs from MG muscle proliferated and differentiated more actively than SCs from healthy muscles. During these processes, MyoD and MyoG were expressed at a higher level in MG SCs.
Additionally, MyoD and MyoG also expressed at a higher level in MG muscle biopsies.
These results suggest that MyoD and MyoG could be responsible for the functional differences observed in SCs from MG compared to healthy muscles. We also show that SCs from healthy muscles and treated with MG sera or monoclonal AChR antibodies differentiated more and expressed more MyoG mRNA than those treated with Ctrl sera or isotype antibodies.
These results suggest that increased differentiation and MyoG expression could be due to the anti-‐AChR antibodies present in the MG sera. Therefore, AChR antibodies could play a key role in the SCs differentiation via the modulation of MyoG expression.
Altogether, these findings demonstrate that the autoimmune attack in MG might lead to important changes in the function of SCs that could represent a mechanism of compensation to regenerate muscle fibres that have been damaged by the autoantibodies or maintain muscle mass.