Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy.
Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as alpha-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, alpha-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy.
Lamon
Séverine
S
Clinique Romande de Réadaptation SUVA Care, Sion 1951, Switzerland.
Wallace
Marita A
MA
Léger
Bertrand
B
Russell
Aaron P
AP
D000328:Adult; D015308:Anaerobic Threshold / Q000502:physiology; D001284:Atrophy; D015153:Blotting, Western; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology; D006801:Humans; D006984:Hypertrophy; D008297:Male; D008840:Microfilament Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000502:physiology; D010101:Oxygen Consumption; D010807:Physical Endurance / Q000502:physiology; D010809:Physical Fitness / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D026362:Serum Response Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014057:Tomography, X-Ray Computed; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D014891:Weight Lifting / Q000502:physiology
C464441:ABRA protein, human; D017931:DNA Primers; D004268:DNA-Binding Proteins; C431575:MRTFA protein, human; D008840:Microfilament Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors