High mobility group box 2 regulates skeletal muscle development through ribosomal protein S6 kinase 1
High mobility group box 2 regulates skeletal muscle development through ribosomal protein S6 kinase 1
复制标题
高迁移率族盒 2 通过核糖体蛋白 S6 激酶 1 调节骨骼肌发育
DOI：
10.1096/fj.202001183r
复制
发表时间：
2020-07-20
期刊：
影响因子：
4.8
通讯作者：
Mo，Delin
中科院分区：
文献类型：
--
作者：
Fang，Ying;Liang，Feng;Mo，Delin
HMGB 2是一种DNA结合蛋白，在胚胎发育过程中高度表达，在某些器官和组织的发育中起重要作用。然而，HMGB 2是否影响肌肉发育还有待进一步研究。在这项工作中，我们确定了HMGB 2作为肌生成的重要因素。与野生型（WT）小鼠相比，系统性hmgb 2纯合敲除（hmgb 2 −/−）小鼠的体重降低，尤其是雄性。在hmgb 2 −/−小鼠中，胫骨前肌（TA）肌纤维的直径和横截面积以及Myogenin和MyHC的表达均降低。CTX损伤模型显示，HMGB 2是卫星细胞增殖和肌肉再生所必需的。此外，HMGB 2与S6 K1相互作用，并在细胞增殖过程中调节S6 K1的激酶活性。C2 C12细胞中S6 K1的敲低和失活均导致增殖和分化受损。HMGB 2和S6 K1基因敲除后，细胞周期蛋白D1和Myf 5的表达均下降，S6 K1激酶活性受到抑制。这些结果表明，HMGB 2是骨骼肌发育和再生所必需的，HMGB 2通过调节S6 K1激酶活性维持成肌细胞的增殖。
HMGB2, a DNA‐binding protein, highly expresses during embryogenesis and plays an important role in development of some organs and tissues. However, it remains to be further investigated weather HMGB2 influences muscle development. In this work, we identified HMGB2 as an essential factor in myogenesis. Compared to wild type (WT) mice, body weights of systemichmgb2homozygous knockout (hmgb2−/−) mice especially males were reduced. Diameter and cross‐section area of tibialis anterior (TA) muscle fibers as well as expression of Myogenin and MyHC were all decreased inhmgb2−/−mice. CTX injury model revealed that HMGB2 was required for satellite cell proliferation and muscle regeneration. Moreover, HMGB2 interacted with S6K1 and regulated the kinase activity of S6K1 during cell proliferation. Knockdown and inactivation of S6K1 in C2C12 cells both resulted in impaired proliferation and differentiation. Furthermore, expression of cyclin D1 and Myf5 were both decreased when HMGB2 or S6K1 were knocked down and kinase activity of S6K1 was inhibited. These results indicate that HMGB2 is required for skeletal muscle development and regeneration, and HMGB2 maintains proliferation of myoblasts through regulating kinase activity of S6K1.