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 1 Comprehensive overview of studies using agents to blunt transforming growth factor (TGF)-β signaling

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

Compound	Mechanism of action	Clinical condition	Model organism	Phenotypic findings	Ref
FDA-approved medications
Losartan	AT1^a receptor antagonist (mostly used for hypertension, cardiomyopathies)	MFS^b	Fbn^1C1039G/+ mice	Improved muscle architecture, function and regeneration	[54]
		DMD^c	mdx mice	Improved skeletal, diaphragmatic and cardiac muscle architecture, function and regeneration	[54, 55]
		Muscle Injury	Young^e mice	Decreased fibrosis and improved regeneration	[56]
Suramin	TGF-β1 receptor antagonist (anti-parasitic, anti-neoplasic)	DMD	mdx mice	Decreased fibrosis and prevented decrease in grip strength	[57]
Anti-fibrotic agents
Decorin	Binds to TGF-β1 ligands	Muscle injury	Young mice	Decreased fibrosis, improved regeneration and functional recovery	[61]
		DMD	mdx mice	Decreased collagen type I levels in diaphragm	[62]
γ-Interferon	Induces Smad7 expression	Muscle injury	Young mice	Decreased fibrosis, improved regeneration and functional recovery	[63]
Pirfenidone	TGF-β1 antagonist	DMD	mdx mice	Improved cardiac function, minor alterations on the development of fibrosis, and no improvement in diaphragmatic function	[64, 65]
Halofuginone	Inhibits TGF-β-dependent phosphorylation of Smad3	DMD	mdx mice	Decreased fibrosis and improved function of the heart,diaphragm and limb muscles	[66, 67]
		CMD^d	dy ^2J /dy ^2J	Decreased fibrosis and improved functional performance but did not improve strength	[68]
TGF-β neutralizing antibody
Neutralizes TGF-β (1 and/or 2) ligands		MFS	Fbn^1C1039G/+ mice	Prevented muscle atrophy and improved regeneration	[54]
		DMD	mdx mice	Decreased fibrosis and improved regeneration	[54, 69]
		Sarcopenia	Aged^g mice	Failed to improve regeneration	[70]
TGF-β receptor kinase inhibitor
Decoy receptor composed of extracellular portion of TGF-β receptor II		Sarcopenia	Aged mice	Improved regeneration after direct intramuscular injection	[70]

^aAngiotensin II type 1 receptor.
^bMarfan syndrome.
^cDuchenne muscular dystrophy.
^dCongenital muscular dystrophy.
^eAge ≤ 3 months.
^fAge 3-15 months.
^gAge ≥ 15 months.

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ISSN: 2044-5040

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