Satellite cells deficiency and defective regeneration in dynamin 2-related centronuclear myopathy

Autor(es)

F. Almeida, Camila ^{[1, 2, 3]} ; Bitoun, Marc ^[2] ; Vainzof, Mariz ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Muscle Prot & Comparat Histopathol, Human Genome & Stem Cell Res Ctr, Biosci Inst, Sao Paulo - Brazil

^[2] Sorbonne Univ, INSERM, Inst Myol, Ctr Res Myol, UMRS 974, Paris - France

^[3] Ohio State Univ, Dept Pediat, Ctr Gene Therapy, Nationwide Childrens Hosp, Columbus, OH 43210 - USA

• Tipo de documento: Artigo Científico
• Fonte: FASEB JOURNAL; v. 35, n. 4 APR 2021.
• Citações Web of Science: 0

Resumo

Dynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes and cytoskeleton dynamics. Mutations in the DNM2 gene cause the autosomal dominant centronuclear myopathy (AD-CNM), characterized mainly by muscle weakness and central nuclei. Several defects have been identified in the KI-Dnm2(R465W/+) mouse model of the disease to explain the muscle phenotype, including reduction of the satellite cell pool in muscle, but the functional consequences of this depletion have not been characterized until now. Satellite cells (SC) are the main source for muscle growth and regeneration of mature tissue. Here, we investigated muscle regeneration in the KI-Dnm2(R465W/+) mouse model for AD-CNM. We found a reduced number of Pax7-positive SCs, which were also less activated after induced muscle injury. The muscles of the KI-Dnm2(R465W/+) mouse regenerated more slowly and less efficiently than wild-type ones, formed fewer new myofibers, and did not recover its normal mass 15 days after injury. Altogether, our data provide evidence that the muscle regeneration is impaired in the KI-Dnm2(R465W/+) mouse and contribute with one more layer to the comprehension of the disease, by identifying a new pathomechanism linked to DNM2 mutations which may be involved in the muscle-specific impact occurring in AD-CNM. (AU)

• Processo FAPESP: 17/07376-7 - Investigação do comportamento de celúlas satélite e das vesículas extracelulares na miopatia centronuclear
• Beneficiário: Camila de Freitas Almeida
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 15/18914-4 - Estudo do potencial regenerativo das células satélite na miopatia centronuclear e a capacidade miogênica de suas microvesículas liberadas
• Beneficiário: Camila de Freitas Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado