Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice

@article{Nakatani2008TransgenicEO,
  title={Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice},
  author={Masashi Nakatani and Yuka Takehara and Hiromu Sugino and Mitsuru Matsumoto and Osamu Hashimoto and Yoshihisa Hasegawa and Tatsuya Murakami and Akiyoshi Uezumi and Shin’ichi Takeda and Sumihare Noji and Yoshihide Sunada and Kunihiro Tsuchida},
  journal={The FASEB Journal},
  year={2008},
  volume={22},
  pages={477 - 487}
}
Myostatin is a potent negative regulator of skeletal muscle growth. Therefore, myostatin inhibition offers a novel therapeutic strategy for muscular dystrophy by restoring skeletal muscle mass and suppressing the progression of muscle degeneration. The known myostatin inhibitors include myostatin propeptide, follistatin, follistatin‐related proteins, and myostatin antibodies. Although follistatin shows potent myostatin‐inhibiting activities, it also acts as an efficient inhibitor of activins… Expand
Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis.
TLDR
In conclusion, inhibiting myostatin with a follistatin-derived peptide provides a novel therapeutic option to decrease adipocyte size, prevent obesity and hepatic steatosis, and improve glucose tolerance. Expand
Expression of Myostatin and Follistatin in Mdx Mice, an Animal Model for Muscular Dystrophy
TLDR
Follistatin not only blocks myostatin but also allows other activators to function in muscle development, emphasizing that follistatin could be a very potent molecule in combating muscle loss during dystrophies and muscle ageing, disuse, or denervation. Expand
Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice.
  • K. Tsuchida
  • Biology, Medicine
  • Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology
  • 2008
TLDR
Data indicate that myostatin inhibition by this follistatin-derived peptide has therapeutic potential for muscular dystrophy. Expand
Myostatin and activin blockade by engineered follistatin results in hypertrophy and improves dystrophic pathology in mdx mouse more than myostatin blockade alone
TLDR
In wild-type and mdx mice, dose-dependent increases in muscle mass and quadriceps myofiber size were observed for engineered follistatin and hypertrophy and anti-fibrotic effects in the mdx model were generated. Expand
Evaluation of follistatin as a therapeutic in models of skeletal muscle atrophy associated with denervation and tenotomy
TLDR
The delivery of a recombinant adeno-associated viral vector expressing follistatin to the hind-limb musculature of mice two weeks prior to denervation or tenotomy promoted muscle hypertrophy that was sufficient to preserve muscle mass comparable to that of untreated sham-operated muscles, demonstrating that the anabolic effects of follistin are influenced by the interaction between muscle fibres and motor nerves. Expand
Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy
TLDR
It is shown that myostatin inhibition by follistatin transgene expression in Dysf−/− mice results in early improvement in histopathology but ultimately exacerbates muscle degeneration; this effect was not observed in dystrophin-deficient (mdx) mice, suggesting that accelerated degeneration induced by follistsin transGene expression is specific to mice lacking dysferlin. Expand
Systemic Myostatin Inhibition via Liver-Targeted Gene Transfer in Normal and Dystrophic Mice
TLDR
Systemic myostatin inhibition led to increased skeletal muscle mass and strength in control C57 Bl/6 mice and in the dystrophin-deficient mdx model of Duchenne muscular dystrophy, and Liver-targeted gene transfer of aMyostatin inhibitor provides novel insights into the long-term effects and shortcomings of mystatin inhibition on striated muscle. Expand
The function of Activin receptor type IIb signaling in adult skeletal muscle
Myostatin, a growth factor of the TGF-β family that signals through the activin receptor-IIB (ActRIIB), has been identified as an important negative regulator of skeletal muscle growth. However, itsExpand
A GDF11/myostatin inhibitor, GDF11 propeptide-Fc, increases skeletal muscle mass and improves muscle strength in dystrophic mdx mice
TLDR
GDF11PRO-Fc induces skeletal muscle hypertrophy and improvements in muscle strength via inhibition of GDF11/myostatin signaling, but does not significantly improve the dystrophic pathology in mdx mice. Expand
A new protein curbs the hypertrophic effect of myostatin inhibition, adding remarkable endurance to motor performance in mice
TLDR
Results are consistent with published observations that endurance training in rats increased acetylcholine receptor quantity at neuromuscular junctions and provide evidence that improving nerve-muscle interaction could be an important factor for sustaining long term muscle activity. Expand
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