Open AccessIrisin promotes C2C12 myoblast proliferation via ERK-dependent CCL7 upregulation
Author(s) -
Jangho Lee,
Joon Park,
Young Ho Kim,
Nam Hyouck Lee,
KyungMo Song
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0222559
Subject(s) - c2c12 , mapk/erk pathway , myocyte , cell growth , ccl7 , downregulation and upregulation , microbiology and biotechnology , signal transduction , biology , myogenesis , endocrinology , biochemistry , receptor , chemokine receptor , chemokine , gene
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.