HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2.
Although the mechanism underlying modulation of transcription factors in myogenesis has been well elucidated, the function of the transcription cofactors involved in this process remains poorly understood. Here, we identified HMGB2 as an essential nuclear transcriptional co-regulator in myogenesis. HMGB2 was highly expressed in undifferentiated myoblasts and regenerating muscle. Knockdown of HMGB2 inhibited myoblast proliferation and stimulated its differentiation. HMGB2 depletion downregulated Myf5 and cyclin A2 at the protein but not mRNA level. In contrast, overexpression of HMGB2 promoted Myf5 and cyclin A2 protein upregulation. Furthermore, we found that the RNA-binding protein IGF2BP2 is a downstream target of HMGB2, as previously shown for HMGA2. IGF2BP2 binds to mRNAs of Myf5 or cyclin A2, resulting in translation enhancement or mRNA stabilization, respectively. Notably, overexpression of IGF2BP2 could partially rescue protein levels of Myf5 and cyclin A2, in response to HMGB2 decrease. Moreover, depletion of HMGB2 in vivo severely attenuated muscle repair; this was due to a decrease in satellite cells. Taken together, these results highlight the previously undiscovered and crucial role of the HMGB2-IGF2BP2 axis in myogenesis and muscle regeneration.
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Xingyu
0000-0001-7589-9928
X
Zhou
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Mingsen
0000-0003-3019-3387
M
Li
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Huaxing
0000-0001-6455-676X
H
Huang
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Keren
0000-0002-3871-7651
K
Chen
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Zhuning
0000-0001-6192-6905
Z
Yuan
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Ying
0000-0002-5861-2355
Y
Zhang
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Yaping
0000-0003-4456-0651
Y
Nie
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Hu
0000-0001-8136-7442
H
Chen
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Xumeng
X
Zhang
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
Luxi
0000-0001-7802-9215
L
Chen
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China modelin@mail.sysu.edu.cn chyaosh@mail.sysu.edu.cn.
Yaosheng
0000-0002-3871-7651
Y
Chen
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510006, China modelin@mail.sysu.edu.cn chyaosh@mail.sysu.edu.cn.
Delin
0000-0002-8738-4486
D
Mo
D000818:Animals; D000831:Animals, Newborn; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D024261:HMGB2 Protein / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*
D018797:Cell Cycle Proteins; D056751:Cyclin A2; D024261:HMGB2 Protein; C559768:IGF2BP2 protein, mouse; D051787:Myogenic Regulatory Factor 5; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
HMGB2; IGF2BP2; Muscle regeneration; Myogenesis