Open AccessNew Role for Serum Response Factor in Postnatal Skeletal Muscle Growth and Regeneration via the Interleukin 4 and Insulin-Like Growth Factor 1 Pathways
Author(s) -
Claude Charvet,
Christophe Houbron,
Ara Parlakian,
Julien Giordani,
Charlotte Lahoute,
Anne T. Bertrand,
Athanassia Sotiropoulos,
Laure Renou,
Alain Schmitt,
Judith Melki,
Zhenlin Li,
Dominique Daegelen,
David Tuil
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00138-06
Subject(s) - serum response factor , biology , skeletal muscle , myocyte , sarcomere , growth factor , insulin like growth factor , endocrinology , medicine , regeneration (biology) , microbiology and biotechnology , gene expression , downregulation and upregulation , gene , receptor , genetics
Serum response factor (SRF) is a crucial transcriptional factor for muscle-specific gene expression. We investigated SRF function in adult skeletal muscles, using mice with a postmitotic myofiber-targeted disruption of theSRF gene. Mutant mice displayed severe skeletal muscle mass reductions due to a postnatal muscle growth defect resulting in highly hypotrophic adult myofibers. SRF-depleted myofibers also failed to regenerate following injury. Muscles lacking SRF had very low levels ofmuscle creatine kinase andskeletal alpha-actin (SKA ) transcripts and displayed other alterations to the gene expression program, indicating an overall immaturity of mutant muscles. This loss ofSKA expression, together with a decrease inbeta-tropomyosin expression, contributed to myofiber growth defects, as suggested by the extensive sarcomere disorganization found in mutant muscles. However, we observed a downregulation ofinterleukin 4 (IL-4 ) andinsulin-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 crucial role for SRF in pathways involved in muscle growth and regeneration.