Abstract
Irisin is an exercise-induced myokine that has various physiological functions, such as roles in energy expenditure, glucose/lipid metabolism, and muscle development. In muscle development, myoblast proliferation is known to be a first step, and recent studies have reported that an increased irisin level is involved in the promotion of cell proliferation in various cell types, including myoblasts. However, the exact mechanism of action by which irisin promotes myoblast proliferation has not been reported. In this study, we aimed to determine the pro-proliferative effect of irisin on C2C12 myoblasts and its mechanism of action. Irisin induced C2C12 cell proliferation and upregulated the mRNA levels of markers of proliferation Pcna, Mki67, and Mcm2. Irisin increased extracellular signal-regulated kinase (ERK) phosphorylation, and U0126, an ERK pathway inhibitor, suppressed irisin-induced C2C12 cell proliferation. Transcriptomic and qRT-PCR analysis showed that Ccl2, Ccl7, Ccl8, and C3 are potential downstream regulators of ERK signaling that promote C2C12 cell proliferation. Knockdown of Ccl7 revealed that irisin upregulates chemokine (C-C motif) ligand 7 (CCL7) and subsequently promotes C2C12 cell proliferation. These results suggest that irisin promotes C2C12 myoblast proliferation via ERK-dependent CCL7 upregulation and may aid in understanding how irisin contributes to muscle development.
Highlights
Irisin is a recently identified myokine that is induced by exercise and stimulates brown-fat-like development of white fat and energy expenditure in humans and mice [1, 2]
Irisin significantly increased the mRNA expression of the genes encoding Proliferating cell nuclear antigen (PCNA) (Pcna), Ki-67 (Mki67), and maintenance complex component 2 (MCM2) (Mcm2) in C2C12 cells (Fig 1C)
The recently identified protein irisin is an exercise-induced myokine involved in the mechanism of the effects of exercise on weight reduction [2], insulin resistance [17], and skeletal muscle development [8]
Summary
Irisin is a recently identified myokine that is induced by exercise and stimulates brown-fat-like development of white fat and energy expenditure in humans and mice [1, 2]. Irisin and myoblast proliferation oxidative stress, in various organs. Several studies have shown that irisin promotes the proliferation of endothelial cells [4] and osteoblasts [5]. Irisin induces myogenesis and mitochondrial biogenesis and protects against muscle atrophy and bone loss [6], and a recent study has reported that irisin promotes C2C12 cell proliferation [7, 8]. The mechanisms of action involved in irisin-induced proliferation of C2C12 myoblasts have not been elucidated
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