title: New role for serum response factor in postnatal skeletal muscle growth and regeneration via the interleukin 4 and insulin-like growth factor 1 pathways.
abstract: 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 the SRF 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 of muscle creatine kinase and skeletal alpha-actin (SKA) transcripts and displayed other alterations to the gene expression program, indicating an overall immaturity of 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 in mutant 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 crucial role for SRF in pathways involved in muscle growth and regeneration.
authors.affiliation: Institut Cochin, Faculté de Médecine Cochin Port Royal, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Charvet
authors.forename: Christophe
authors.initials: C
authors.lastname: Houbron
authors.forename: Ara
authors.initials: A
authors.lastname: Parlakian
authors.forename: Julien
authors.initials: J
authors.lastname: Giordani
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lahoute
authors.forename: Anne
authors.initials: A
authors.lastname: Bertrand
authors.forename: Athanassia
authors.initials: A
authors.lastname: Sotiropoulos
authors.forename: Laure
authors.initials: L
authors.lastname: Renou
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.forename: Judith
authors.initials: J
authors.lastname: Melki
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Li
authors.forename: Dominique
authors.initials: D
authors.lastname: Daegelen
authors.forename: David
authors.initials: D
authors.lastname: Tuil
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D019426:Integrases / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development* / Q000502:physiology* / Q000648:ultrastructure; D009929:Organ Size; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D012518:Sarcomeres / Q000473:pathology / Q000648:ultrastructure; D026362:Serum Response Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D026362:Serum Response Factor; D015847:Interleukin-4; D007334:Insulin-Like Growth Factor I; C045073:Cre recombinase; D019426:Integrases