In skeletal muscle, the Hippo effector Yap promotes satellite cell, myoblast, and rhabdomyoblast proliferation but prevents myogenic differentiation into multinucleated muscle fibres. We previously noted that Yap drives expression of the first enzyme of the serine biosynthesis pathway, phosphoglycerate dehydrogenase (Phgdh). Here, we examined the regulation and function of Phgdh in satellite cells and myoblasts and found that Phgdh protein increased during satellite cell activation. Analysis of published data reveal that Phgdh mRNA in mouse tibialis anterior muscle was highly expressed at day 3 of regeneration after cardiotoxin injection, when markers of proliferation are also robustly expressed and in the first week of synergist-ablated muscle. Finally, siRNA-mediated knockdown of PHGDH significantly reduced myoblast numbers and the proliferation rate. Collectively, our data suggest that Phgdh is a proliferation-enhancing metabolic enzyme that is induced when quiescent satellite cells become activated.

在骨骼肌中，Hippo 效应子 Yap 促进卫星细胞、成肌细胞和横纹肌细胞增殖，但阻止生肌分化为多核肌纤维。我们之前注意到 Yap 驱动丝氨酸生物合成途径的第一种酶磷酸甘油酸脱氢酶 ( Phgdh ) 的表达。在这里，我们检查了Phgdh在卫星细胞和成肌细胞中的调节和功能，发现Phgdh蛋白在卫星细胞激活过程中增加。对已发表数据的分析表明，小鼠胫骨前肌中的Phgdh mRNA 在注射心脏毒素后再生第 3 天时高度表达，此时增殖标记物也强烈表达，并且在增效剂消融肌肉的第一周也出现强烈表达。最后，siRNA 介导的 PHGDH 敲低显着降低了成肌细胞数量和增殖率。总的来说，我们的数据表明 Phgdh 是一种增殖增强代谢酶，当静止卫星细胞被激活时会被诱导。