A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse
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 e...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/7043429 |
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| author | Craig Robert Wright Giselle Larissa Allsopp Alex Bernard Addinsall Natasha Lee McRae Sofianos Andrikopoulos Nicole Stupka |
| author_facet | Craig Robert Wright Giselle Larissa Allsopp Alex Bernard Addinsall Natasha Lee McRae Sofianos Andrikopoulos Nicole Stupka |
| author_sort | Craig Robert Wright |
| collection | DOAJ |
| description | 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 (mdx:Seps1−/+) were generated. The mdx:Seps1−/+ 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-β1 (Tgf-β1) (P=0.056) were increased in mdx:Seps1−/+ 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. |
| format | Article |
| id | doaj-art-95dacdaaf7cf46949517e280cfb99bb1 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-95dacdaaf7cf46949517e280cfb99bb12025-02-03T01:30:53ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/70434297043429A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic MouseCraig Robert Wright0Giselle Larissa Allsopp1Alex Bernard Addinsall2Natasha Lee McRae3Sofianos Andrikopoulos4Nicole Stupka5Institute for Physical Activity and Nutrition Research (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, AustraliaInstitute for Physical Activity and Nutrition Research (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, VIC, AustraliaMolecular Medical Research SRC, School of Medicine, Deakin University, Geelong, VIC, AustraliaMolecular Medical Research SRC, School of Medicine, Deakin University, Geelong, VIC, AustraliaDepartment of Medicine, The University of Melbourne, Melbourne, VIC, AustraliaMolecular Medical Research SRC, School of Medicine, Deakin University, Geelong, VIC, AustraliaExcessive 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 (mdx:Seps1−/+) were generated. The mdx:Seps1−/+ 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-β1 (Tgf-β1) (P=0.056) were increased in mdx:Seps1−/+ 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.http://dx.doi.org/10.1155/2017/7043429 |
| spellingShingle | Craig Robert Wright Giselle Larissa Allsopp Alex Bernard Addinsall Natasha Lee McRae Sofianos Andrikopoulos Nicole Stupka A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse Mediators of Inflammation |
| title | A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse |
| title_full | A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse |
| title_fullStr | A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse |
| title_full_unstemmed | A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse |
| title_short | A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse |
| title_sort | reduction in selenoprotein s amplifies the inflammatory profile of fast twitch skeletal muscle in the mdx dystrophic mouse |
| url | http://dx.doi.org/10.1155/2017/7043429 |
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