JAK2/STAT2/STAT3 are required for myogenic differentiation.
Skeletal muscle satellite cell-derived myoblasts are mainly responsible for postnatal muscle growth and injury-induced regeneration. However, the cellular signaling pathways that control proliferation and differentiation of myoblasts remain poorly defined. Recently, we found that JAK1/STAT1/STAT3 not only participate in myoblast proliferation but also actively prevent them from premature differentiation. Unexpectedly, we found that a related pathway consisting of JAK2, STAT2, and STAT3 is required for early myogenic differentiation. Interference of this pathway by either a small molecule inhibitor or small interfering RNA inhibits myogenic differentiation. Consistently, all three molecules are activated upon differentiation. The pro-differentiation effect of JAK2/STAT2/STAT3 is partially mediated by MyoD and MEF2. Interestingly, the expression of the IGF2 gene and the HGF gene is also regulated by JAK2/STAT2/STAT3, suggesting that this pathway could also promote differentiation by regulating signaling molecules known to be involved in myogenic differentiation. In summary, our current study reveals a novel role for the JAK2/STAT2/STAT3 pathway in myogenic differentiation.
Wang
Kepeng
K
Department of Biochemistry, Hong Kong University of Science & Technology, Clearwater Bay, Kowloon, Hong Kong, China.
Wang
Chihao
C
Xiao
Fang
F
Wang
Haixia
H
Wu
Zhenguo
Z
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D053614:Janus Kinase 2 / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D024510:Muscle Development; D032446:Myoblasts / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction
D034741:RNA, Small Interfering; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494085:Stat2 protein, mouse; C494087:Stat3 protein, mouse; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2