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Role of JAK3 in myogenic differentiation

Authors
Jang, YN; Lee, IJ; Park, MC; Baik, EJ
Citation
Cellular signalling, 24(3):742-749, 2012
Journal Title
Cellular signalling
ISSN
0898-65681873-3913
Abstract
Skeletal muscle differentiation is regulated by transcription factors, including members of the myogenic regulatory factor (MRF) family and many signaling pathways. The JAK1 and JAK2 pathways are known to each have different effects on myoblast proliferation and differentiation; however, the role of JAK3 in myoblast differentiation remains unclear. In this study, we investigated the effect of JAK3 inhibition on myogenic differentiation in the C2C12 mouse myoblast cell line. During myogenic differentiation, treatment with the JAK3 inhibitor WHIp154 significantly increased the number of MHC-positive multinucleated myotubes and the expressions of myosin heavy chain (MHC), myogenin (MGN), MyoD, and myogenic enhancer factor 2 (MEF2). Knockdown of the JAK3 gene using siJAK3 also significantly increased MHC, MGN and MyoD mRNA expressions as well as insulin-like growth factor-II (IGF-II) gene expression. During differentiation, JAK3 was initially activated and later decreased. Differentiation decreased STAT1, which was further decreased by WHIp154. In contrast, STAT3 gradually was elevated during differentiation, and was increased by JAK3 inhibition. Moreover, we found that up-regulation of AKT activity and down-regulation of ERK activity cooperated to accelerate myogenic differentiation. Taken together, these data indicate that JAK3 inhibition potently facilitates myoblast differentiation through antagonistic STAT1/STAT3 activities. Additionally, JAK3 inhibition induced precocious differentiation and played important roles for terminal differentiation, including fusion, which is involved with regulation of AKT and ERK pathways.
MeSH terms
Animals*Cell DifferentiationCell LineInsulin-Like Growth Factor II/genetics/metabolismJanus Kinase 3/antagonists & inhibitors/*metabolismMAP Kinase Signaling SystemMiceMyoD Protein/genetics/metabolismMyoblasts/*cytology/*enzymologyMyogenic Regulatory Factors/genetics/metabolismMyogenin/genetics/metabolismMyosin Heavy Chains/genetics/metabolismQuinazolines/chemistry/pharmacologyRNA InterferenceRNA, Small Interfering/metabolismSTAT1 Transcription Factor/metabolismSTAT3 Transcription Factor/metabolism
DOI
10.1016/j.cellsig.2011.11.009
PMID
22120524
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Plastic & Reconstructive Surgery
AJOU Authors
장, 유나이, 일재박, 명철백, 은주
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