Early Activation of Rat Skeletal Muscle IL-6/STAT1/STAT3 Dependent Gene Expression in Resistance Exercise Linked to Hypertrophy

Abstract

Cytokine interleukin-6 (IL-6) is an essential regulator of satellite cell-mediated hypertrophic muscle growth through the transcription factor signal transducer and activator of transcription 3 (STAT3). The importance of this pathway linked to the modulation of myogenic regulatory factors expression in rat skeletal muscle undergoing hypertrophy following resistance exercise, has not been investigated. In this study, the phosphorylation and nuclear localization of STAT3, together with IL-6/STAT3-responsive gene expression, were measured after both a single bout of resistance exercise and 10 weeks of training. Flexor Digitorum Profundus muscle samples from Wistar rats were obtained 2 and 6 hours after a single bout of resistance exercise and 72 h after the last bout of either 2, 4, or 10 weeks of resistance training. We observed an increase in IL-6 and SOCS3 mRNAs concomitant with phosphorylation of STAT1 and STAT3 after 2 and 6 hours of a single bout of exercise (p<0.05). STAT3-dependent early responsive genes such as CyclinD1 and cMyc were also upregulated whereas MyoD and Myf5 mRNAs were downregulated (p<0.05). BrdU-positive satellite cells increased at 2 and 6 hours after exercise (p<0.05). Muscle fiber hypertrophy reached up to 100% after 10 weeks of training and the mRNA expression of Myf5, c-Myc and Cyclin-D1 decreased, whereas IL-6 mRNA remained upregulated. We conclude that the IL-6/STAT1/STAT3 signaling pathway and its responsive genes after a single bout of resistance exercise are an important event regulating the SC pool and behavior involved in muscle hypertrophy after ten weeks of training in rat skeletal muscle.

Lewis lung carcinoma regulation of mechanical stretch-induced protein synthesis in cultured myotubes

“…The IL-6 cytokines play an enigmatic role in skeletal mass regulation (39). They are secreted by muscle fibers during exercise or overload and are involved in muscle hypertrophy and regeneration by stimulating satellite cell proliferation (5,45,56,60). However, they are involved in muscle wasting during cancer cachexia.…”

“…The IL-6 family of cytokines has a documented role in skeletal muscle mass regulation (39). Skeletal muscle expression of IL-6 and leukemia inhibitory factor (LIF) are induced by exercise (8,45), and both IL-6 and LIF can regulate overloadinduced muscle hypertrophy (5,59). A role of gp130-initiated signaling for mechanical regulation of muscle protein synthesis has not been established.…”

Intramuscular MAPK signaling following high volume and high intensity resistance exercise protocols in trained men

“…STAT1 is activated by ERK1/2 and serves as a downstream nuclear transcription factors involved in muscle remodeling (Farooq and Zhou 2004;Guan 1994). An increase in STAT1 phosphorylation has been observed following a single bout of resistance exercise in rat skeletal muscle, and has been proposed to play a role in satellite cell proliferation (Begue et al 2013). However, STAT1 phosphorylation has also shown to be unaltered following 3 sets of 12 repetitions of maximal single-leg knee extensions in young men (Trenerry et al 2011).…”

Effects of long-term resistance exercise training on autophagy in rat skeletal muscle of chloroquine-induced sporadic inclusion body myositis

“…Thus, we aimed to establish a protocol applicable to subjects with muscle disease in our previous test. Referencing existing protocols [39][40][41][42], our modified method was accomplished successfully. The workout equipment consisting of climbing ladders (20 × 115 cm) with 4 cm grids inclined at 85 degrees were made in our laboratory.…”