The extracellular matrix differentially directs myoblast motility in distinct forms of muscular dystrophy

biorxiv(2023)

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摘要
Extracellular matrix (ECM) pathologic remodeling underlies many fibrotic disorders, including muscular dystrophy. Tissue decellularization removes cellular components while leaving behind ECM components. We generated “on-slide” decellularized tissue slices from genetically distinct dystrophic mouse models. The ECM of dystrophin-and sarcoglycan-deficient muscles had marked thrombospondin 4 deposition, while dysferlin-deficient muscle had excess decorin. Annexins A2 and A6 were present on all dystrophic decellularized ECMs, but annexin matrix deposition was excessive in dysferlin-deficient muscular dystrophy. Adeno-associated viral expression of annexin A6 specifically in muscle resulted in annexin A6 deposition throughout the ECM, indicating muscle as a source of this ECM protein. C2C12 myoblasts seeded onto decellularized matrices displayed differential myoblast mobility. Dystrophin-deficient decellularized matrices inhibited myoblast mobility while dysferlin-deficient decellularized matrices enhanced myoblast movement. Myoblasts treated with recombinant annexin A6 increased mobillity similar to that seen on dysferlin-deficient decellularized matrix. These findings demonstrate specific fibrotic signatures elicit effects on myoblast activity. TEASER Fibrosis in muscular dystrophy has differential effects on myoblasts HIGHLIGHTS ### Competing Interest Statement The authors have declared no competing interest. * (ECM) : Extracellular matrix (dECM) : decellularized extracellular matrix (DMD) : Duchenne Muscular Dystrophy (LGMD) : Limb Girdle Muscular Dystrophy (SDS) : sodium dodecyl sulfate
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