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Πέμπτη 8 Απριλίου 2021

Persistent mdx diaphragm alterations are accompanied by increased expression and activity of calcium and muscle-specific proteins

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Histol Histopathol. 2021 Apr 7:18334. doi: 10.14670/HH-18-334. Online ahead of print.

ABSTRACT

The mdx mouse model of Duchenne Muscular Dystrophy (DMD) presents sarcolemma instability and develops a mild multi-stage dystrophinopathy characterized by intense myonecrosis with inflammatory infiltrate at 4-weeks; muscular regeneration at 12-weeks and persistent fibrosis onwards. Mdx diaphragm muscle has a more severe phenotype with structural and functional deterioration that closely resembles the diaphragm impairment responsible for DMD human patients' morbidity. Herein, we compared calcium deposits, activity of calcium-related proteases, and expression of muscle-specific proteins in mdx diaphragm at 4-weeks and 12-weeks. We found increased calcium deposits mainly at 12-weeks, concomitant with high activity of calpains and matrix metaloprotease-9, but decreased expression of Myhc4 (Myhc IIb) and Atpa2a1 (SERCA1), and high expression of th e myogenic regulatory factors Myod1 and Myog. Our results suggest that increased calcium deposits and persistent activity of calcium dependent proteases throughout the disease are involved in the degeneration and regeneration processes in the mdx diaphragm.

PMID:33825181 | DOI:10.14670/HH-18-334

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