Regulation of STARS and its downstream targets suggest a novel pathway involved in human skeletal muscle hypertrophy and atrophy

Abstract

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.

Figure 1. Effect of 8 weeks of resistance training (Post-Tr) and 8 weeks of de-training (Post-DeTr) on STARS mRNA and RhoA protein content

Significantly different from pre-training and 8 weeks post-training levels: ^*P < 0.05; ^**P < 0.01.

Figure 2. Effect of 8 weeks of resistance training (Post-Tr) and 8 weeks of de-training (Post-DeTr) on MRTF-A, MRTF-B and SRF mRNA expression as well as on SRF protein levels

Significantly different from pre-training and 8 weeks post-training levels: ^*P < 0.05; ^**P < 0.01; ^***P < 0.005.

Figure 3. Regulation of α-actin, MHCIIa and IGF-1 mRNA expression following 8 weeks of resistance training (Post-Tr) and 8 weeks of de-training (Post-DeTr)

^*Significantly different from pre-training levels: P < 0.05; #significantly different from post-training levels: P < 0.05.