A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse.
Mediators Inflamm
; 2017: 7043429, 2017.
Article
em En
| MEDLINE
| ID: mdl-28592916
ABSTRACT
Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S (Seps1) are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion (mdxSeps1-/+) were generated. The mdxSeps1-/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL) muscles, mRNA expression of monocyte chemoattractant protein 1 (Mcp-1) (P = 0.034), macrophage marker F4/80 (P = 0.030), and transforming growth factor-ß1 (Tgf-ß1) (P = 0.056) were increased in mdxSeps1-/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
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Fibras Musculares de Contração Rápida
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Fibras Musculares Esqueléticas
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Distrofia Muscular de Duchenne
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Selenoproteínas
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Proteínas de Membrana
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Contração Muscular
Limite:
Animals
Idioma:
En
Revista:
Mediators Inflamm
Assunto da revista:
BIOQUIMICA
/
PATOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Austrália