Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation

Sen Wei Tsai, Yu Tang Tung, Hsiao Ling Chen, Shang Hsun Yang, Chia Yi Liu, Michelle Lu, Hui Jing Pai, Chi Chen Lin, Chuan Mu Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aim Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. Main methods In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Key findings Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles (p < 0.05). And enhancement of the gene expression of the muscle regulatory factors, neurite outgrowth factors (IGF-1, GAP43) and acetylcholine receptors was observed. Our results demonstrate that myostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Significance Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalLife Sciences
Volume146
DOIs
Publication statusPublished - Feb 1 2016
Externally publishedYes

Fingerprint

Myostatin
Muscular Atrophy
Botulinum Toxins
Firearms
Denervation
Muscle
Rats
Genes
Muscles
Cholinergic Receptors
Gene Expression
Gene expression
Myogenic Regulatory Factors
IGF Type 1 Receptor
Neuromuscular Junction
Nerve Growth Factors
Genetic Therapy
Transcriptional Activation
Gene therapy
Insulin-Like Growth Factor I

Keywords

  • Acetylcholine receptor
  • Gene therapy
  • Muscle atrophy
  • Muscle regulatory factors
  • Myostatin propeptide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation. / Tsai, Sen Wei; Tung, Yu Tang; Chen, Hsiao Ling; Yang, Shang Hsun; Liu, Chia Yi; Lu, Michelle; Pai, Hui Jing; Lin, Chi Chen; Chen, Chuan Mu.

In: Life Sciences, Vol. 146, 01.02.2016, p. 15-23.

Research output: Contribution to journalArticle

Tsai, Sen Wei ; Tung, Yu Tang ; Chen, Hsiao Ling ; Yang, Shang Hsun ; Liu, Chia Yi ; Lu, Michelle ; Pai, Hui Jing ; Lin, Chi Chen ; Chen, Chuan Mu. / Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation. In: Life Sciences. 2016 ; Vol. 146. pp. 15-23.
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AB - Aim Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. Main methods In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Key findings Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles (p < 0.05). And enhancement of the gene expression of the muscle regulatory factors, neurite outgrowth factors (IGF-1, GAP43) and acetylcholine receptors was observed. Our results demonstrate that myostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Significance Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy.

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