Impact of SOCS3 overexpression on human skeletal muscle development in vitro

The Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling cascade has been identified as a crucial factor for myogenesis. The STAT3 isoform is essential for satellite cell migration and myogenic differentiation as it mediates the expression of muscle specific myogenic factors. The SOCS (suppressors of cytokine signaling) family of proteins down-regulates STAT activation. Primary human skeletal muscle cells were isolated and cultured to investigate the effect of SOCS3 adenoviral overexpression on myotube maturation. It was demonstrated that STAT3 inhibition did not influence myotube development or survival. Moreover, SOCS3 overexpression enhances the mRNA expression of downstream targets of STAT3, c-FOS and VEGF. These increases were correlated with enhanced mRNA expression of genes associated with muscle maturation and hypertrophy. Thus SOCS3 influences myoblast differentiation and SOCS3 may be significant in regulating the activity of genes previously identified as transcriptionally regulated by STAT3.

► Use of human skeletal muscle cells to investigate SOCS3 overexpression in maturing myotubes.
► SOCS3 overexpression abolished STAT3 phosphorylation.
► STAT3 inhibition does not influence myotube development or survival.
► SOCS3 overexpression enhanced mRNA expression of downstream targets of STAT3, c-FOS and VEGF.
► SOCS3 overexpression increased expression of genes associated with hypertrophy.