Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment

Journal of Cachexia, Sarcopenia and Muscle
Jessica González-SánchezJesús P Camiña

Abstract

This study was performed to test the therapeutic potential of obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to ameliorate the Duchenne muscular dystrophy (DMD) phenotype. Using a multidisciplinary approach, we characterized the ageing-related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4-, 8-, and 18-week-old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8-week-old mdx mice (n = 5/group). The findings were extended to in vitro effects on human immortalized DMD myotubes. An analysis of TAs revealed an age-related loss of preproghrelin expression, as precursor of obestatin, in mdx mice. Administration of obestatin resulted in a significant increase in tetanic specific force (33.0% ± 1.5%, P < 0.05), compared with control mdx mice. Obestatin-treated TAs were characterized by reduction of fibres with centrally located nuclei (10.0% ± 1.2%, P < 0.05) together with an increase in the number of type I fibres (25.2% ± 1.7%, P < 0.05) associated to histone deacetylases/myocyte enhancer factor-2 and peroxisome proliferator-activated receptor-gamma coactivator 1α axis, and down-regulation of ubiquitin E3-ligases by inactivation ...Continue Reading

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Citations

Dec 11, 2019·Journal of Cachexia, Sarcopenia and Muscle·Markus S AnkerStephan von Haehling
Dec 10, 2020·International Journal of Experimental Pathology·Maria Laura Jorge MichelettoDavid Feder
Mar 10, 2021·Journal of Cachexia, Sarcopenia and Muscle·Tania Cid-DíazJesus P Camiña
May 18, 2021·Neuropathology and Applied Neurobiology·Patricia Soblechero-MartínVirginia Arechavala-Gomeza

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Methods Mentioned

BETA
biopsy
electrophoresis
PCR
transgenic

Software Mentioned

GraphPad
ImageJ64
GraphPad Prism

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