Role of TGF-β signaling in inherited and acquired myopathies

Burks, Tyesha N.; Cohn, Ronald D.

doi:10.1186/2044-5040-1-19

Skeletal Muscle

Table 2 Comprehensive overview of studies using post-natal inhibition of myostatin

From: Role of TGF-β signaling in inherited and acquired myopathies

Disease	Model organism	Phenotypic findings	Ref
Neutralizing antibody: binds to active myostatin and prevents receptor binding
DMD^a	mdx mice	Improved regeneration and function, induced hypertrophy, decreased degeneration (diaphragm) and fibrosis	[78, 79]
LGMD2C^b	sgcg^-/- mice	Improved function, induced hypertrophy but no histopathological improvement	[80]
LGMD2F	sgcd^-/- mice	Increased muscle mass, regeneration (young) and fibrosis (aged)	[81]
ALS^c	SOD1^G93A mice and rats	Delayed onset of muscle atrophy and functional decline without extending survival	[82]
Sarcopenia	Aged^f mice	Prevented loss of body weight, muscle mass and function, and decline in physical activity, reduced apoptosis, no change in fibrosis	[44, 83]
Disuse atrophy	Adult^g mice	Partially protected against but did not prevent atrophy	[99]
ActRIIB-Fc ^d : soluble, decoy receptor binding active myostatin
DMD	mdx mice	Increased body weight and function, induced hypertrophy	[84, 100]
LGMD1C	CAV-3^P104L mice	Induced muscle hypertrophy	[85]
SMA^e	SMAΔ7 mice	Modestly increased muscle weight and strength, decreased survival	[86]
ALS	SOD1^G93A mice	Delayed onset of disease but did not extend survival, reduced weakness after onset	[87]
Cachexia	Lewis-lung carcinoma	Protected against loss of body weight and muscle mass	[88]
Cachexia	Colon-26 carcinoma	Protected against or restored loss of body weight, muscle mass and grip strength, and increased survival	[88, 89]
MSTN Propeptide: binds to myostatin and prevents release of active form
DMD	mdx mice	Induced hypertrophy, increased strength, improved histopathological features of limb and diaphragm, decreased endurance, produced adverse effects on cardiomyopathy	[48, 50, 90]
LGMD2A	Capn3^-/- mice	Increased muscle mass and force, no improvement in histopathological features	[91]
LGMD2D	sgca^-/- mice	Insufficient delivery of vector resulted in no hypertrophy or any change in necrosis	[91]
Muscle Injury	Adult mice	Increased muscle mass, improved regeneration, decreased fibrosis	[92]
Follistatin: inhibitory protein that binds to myostatin
SMA	SMAΔ7 mice	Improved muscle mass (during early stages of disease), motor function and extended survival	[93]
ALS	SOD1^G93A mice	Increased muscle mass (hyperplasia) and strength (not performance) but no survival extension	[94]
HDAC Inhibitors: induce expression of follistatin
DMD	mdx mice	Induced hypertrophy, decreased fibrosis and necrosis, restored muscle architecture, increased strength and performance	[95]
LGMD2D	sgca^-/- mice	Induced hypertrophy and reduced fibrosis	[95]
Cachexia	Colon-26 carcinoma	Did not protect against loss of body weight, muscle mass or function	[88, 96]
Muscle injury	Young^h mice	Improved regeneration	[97]
MSTN peptide: dominant negative truncated myostatin peptide that binds ActRIIB
Sarcopenia	Aged mice	Improved grip strength and enhanced inflammatory response after injury	[98]
Muscle injury	Adult mice	Improved regeneration, decrease in necrosis	[98]
Antisense RNA: binds myostatin messenger RNA and inactivates it
Cachexia	S-180 ascitic tumor	Increased muscle mass	[43]

^aDuchenne muscular dystrophy.
^bLimb-girdle muscular dystrophy.
^cAmyotrophic lateral sclerosis.
^dActivin type IIB receptor.
^eSpinal muscular atrophy.
^fAge≥ 15 months.
^gAge 3-15 months.
^hAge ≤ 3 months.

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ISSN: 2044-5040

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