A growth stimulus is needed for IGF-1 to induce skeletal muscle hypertrophy in vivo
| Autor: | Miranda D. Grounds, Thea Shavlakadze, Jinfen Chai, Greg Cozens, Nadine Winn, Kirsten Maley, Nadia Rosenthal, Griffen Grounds |
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| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty Aging Transgene Muscle Fibers Skeletal P70-S6 Kinase 1 Biology Protein Serine-Threonine Kinases Muscle hypertrophy Mice Internal medicine medicine Animals RNA Messenger Muscular dystrophy Insulin-Like Growth Factor I Phosphorylation Muscle Skeletal Myogenin TOR Serine-Threonine Kinases Body Weight Intracellular Signaling Peptides and Proteins Skeletal muscle Ribosomal Protein S6 Kinases 70-kDa Hypertrophy Organ Size Cell Biology Muscular Dystrophy Animal medicine.disease medicine.anatomical_structure Endocrinology Gene Expression Regulation Mice Inbred mdx Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of Cell Science. 126:4536-4536 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.141143 |
| Popis: | Here, we characterise new strains of normal and dystrophic (mdx) mice that overexpress Class 2 IGF-1 Ea in skeletal myofibres. We show that transgenic mice have increased muscle levels of IGF-1 (approximately 13-26 fold) and show striking muscle hypertrophy (approximately 24-56% increase in mass). Adult normal muscles were resistant to elevated IGF-1; they reached adult steady state and maintained the same mass from 3 to 12 months. By contrast, dystrophic muscles from mdx/IGF-1(C2:Ea) mice continued to increase in mass during adulthood. IGF-1 signalling was evident only in muscles that were growing as a result of normal postnatal development (23-day-old mice) or regenerating in response to endogenous necrosis (adult mdx mice). Increased phosphorylation of Akt at Ser473 was not evident in fasted normal adult transgenic muscles, but was 1.9-fold higher in fasted normal young transgenic muscles compared with age-matched wild-type controls and fourfold higher in fasted adult mdx/IGF-1(C2:Ea) compared with mdx muscles. Muscles of adult mdx/IGF-1(C2:Ea) mice showed higher p70(S6K)(Thr421/Ser424) phosphorylation and both young transgenic and adult mdx/IGF-1(C2:Ea) mice had higher phosphorylation of rpS6(Ser235/236). The level of mRNA encoding myogenin was increased in normal young (but not adult) transgenic muscles, indicating enhanced myogenic differentiation. These data demonstrate that elevated IGF-1 has a hypertrophic effect on skeletal muscle only in growth situations. |
| Databáze: | OpenAIRE |
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