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Life Sci. 2016 Feb 1;146:15-23. doi: 10.1016/j.lfs.2015.12.056. Epub 2016 Jan 5.

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

Author information

1
Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Department of Physical Medicine and Rehabilitation, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung 404, Taiwan; Department of Physical Medicine and Rehabilitation, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
2
Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
3
Department of Bioresources, Da-Yeh University, Changhua 515, Taiwan.
4
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan.
5
Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
6
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan.
7
Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan; Integrative Evolutionary Galliform Genomics (iEGG) Center, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: chchen1@dragon.nchu.edu.tw.

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.

KEYWORDS:

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

PMID:
26764230
DOI:
10.1016/j.lfs.2015.12.056
[Indexed for MEDLINE]

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