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

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• 作者：Sen-Wei Tsai^a ; ^b ; ^c ; Yu-Tang Tung^a ; Hsiao-Ling Chen^d ; Shang-Hsun Yang^e ; ^f ; Chia-Yi Liu^a ; ^g ; Michelle Lu^a ; Hui-Jing Pai^a ; Chi-Chen Lin^h ; Chuan-Mu Chen^a ; ⁱ ; ^j ; ^{chchen1@dragon.nchu.edu.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AChR ; acetylcholine receptor ; BoNT-A ; botulinum toxin A ; cdk ; cyclin-dependent kinase ; CMV ; cytomegalovirus ; DEPC ; diethylpyrocarbonate ; EGFP ; enhanced green fluorescent protein ; GAP-43 ; growth associated protein of 43  ; kDa ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; H&E ; hematoxylin and eosin ; IGF-1 ; insulin-like growth factor I ; MPro ; myostatin propeptide ; MRF4 ; myogenic regulatory factor 4 ; MSPP ; wild-type myostatin propeptide ; MSPPD75A ; mutant-type myostatin propeptide ; Myf5 ; myoge
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：146
• 期：Complete
• 页码：15-23
• 全文大小：1492 K

文摘

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.