Role of IL-6/JAK2/STAT3 signaling in skeletal muscle atrophy

Abstract

Skeletal muscle is the largest organ in the human body and has important roles, including in movement, amino acid storage, glucose uptake, and the secretion of myokines. Various types of insult, including sepsis, burns, and cancer, activate interleukin-6 （IL-6）/janus kinase （JAK） 2/signal transducer and activator of transcription （STAT） 3 signaling and induce skeletal muscle atrophy. The IL-6/JAK2/STAT3 pathway activates proteolytic processes, including the ubiquitin-proteasomal, autophagy, and apoptosis pathways；and inhibits pathways that upregulate protein synthesis, such as the insulin-like growth factor-1 pathway. IL-6/JAK2/STAT3 signaling also inhibits skeletal muscle myogenesis by reducing the activities of regulators of myogenesis. Because the skeletal muscle atrophy induced through these mechanisms adversely affects both the survival and functional outcomes of patients, there is a need to develop novel strategies that target IL-6/JAK2/STAT3 signaling, such as those discussed in this review, as a means of reducing skeletal muscle atrophy.