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New Role for Serum Response Factor in Postnatal Skeletal Muscle Growth and Regeneration via the Interleukin 4 and Insulin-Like Growth Factor 1 Pathways. New Role for Serum Response Factor in Postnatal Skeletal Muscle Growth and Regeneration via the Interleukin 4 and Insulin-Like Growth Factor 1 Pathways: SKELETAL MUSCLE GROWTH, REGENERATION, AND SRF DEFECT
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Edité par CCSD ; American Society for Microbiology -
International audience. Serum response factor (SRF) is a crucial transcriptional factor for muscle-specific gene expression. Weinvestigated SRF function in adult skeletal muscles, using mice with a postmitotic myofiber-targeted disruptionof the SRF gene. Mutant mice displayed severe skeletal muscle mass reductions due to a postnatal musclegrowth defect resulting in highly hypotrophic adult myofibers. SRF-depleted myofibers also failed to regeneratefollowing injury. Muscles lacking SRF had very low levels of muscle creatine kinase and skeletal alpha-actin (SKA)transcripts and displayed other alterations to the gene expression program, indicating an overall immaturityof mutant muscles. This loss of SKA expression, together with a decrease in beta-tropomyosin expression,contributed to myofiber growth defects, as suggested by the extensive sarcomere disorganization found inmutant muscles. However, we observed a downregulation of interleukin 4 (IL-4) and insulin-like growth factor 1(IGF-1) expression in mutant myofibers which could also account for their defective growth and regeneration.Indeed, our demonstration of SRF binding to interleukin 4 and IGF-1 promoters in vivo suggests a new crucialrole for SRF in pathways involved in muscle growth and regeneration.
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