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Supraphysiological levels of GDF11 induce striated muscle atrophy.

ABSTRACT: Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor ? superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the in vivo effects of GDF11 on skeletal muscle mass have not been addressed. Using in vitro myoblast culture assays, we first demonstrate that GDF11 and Mstn have similar activities/potencies on activating p-SMAD2/3 and induce comparable levels of differentiated myotube atrophy. We further demonstrate that adeno-associated virus-mediated systemic overexpression of GDF11 in C57BL/6 mice results in substantial atrophy of skeletal and cardiac muscle, inducing a cachexic phenotype not seen in mice expressing similar levels of Mstn. Greater cardiac expression of Tgfbr1 may explain this GDF11-specific cardiac phenotype. These data indicate that bioactive GDF11 at supraphysiological levels cause wasting of both skeletal and cardiac muscle. Rather than a therapeutic agent, GDF11 should be viewed as a potential deleterious biomarker in muscle wasting diseases.

SUBMITTER: Hammers DW

PROVIDER: S-EPMC5376753 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Supraphysiological levels of GDF11 induce striated muscle atrophy.

Hammers David W DW Merscham-Banda Melissa M Hsiao Jennifer Ying JY Engst Stefan S Hartman James J JJ Sweeney H Lee HL

EMBO molecular medicine 20170401 4

Growth and differentiation factor (GDF) 11 is a member of the transforming growth factor β superfamily recently identified as a potential therapeutic for age-related cardiac and skeletal muscle decrements, despite high homology to myostatin (Mstn), a potent negative regulator of muscle mass. Though several reports have refuted these data, the <i>in vivo</i> effects of GDF11 on skeletal muscle mass have not been addressed. Using <i>in vitro</i> myoblast culture assays, we first demonstrate that G ...[more]

PMID: 28270449

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Supraphysiological levels of GDF11 induce striated muscle atrophy.

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Supraphysiological levels of GDF11 induce striated muscle atrophy.

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