Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration
Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration
复制标题
毛囊干细胞分化过程中线粒体有氧呼吸被激活，其功能障碍会阻碍毛发再生
作者：
Tang, Yan;Luo, Binping;Li, Ji
背景。新兴研究揭示了线粒体通过活性氧（reactive oxygen species， ROS）、Notch等信号通路调控神经祖细胞、间充质干细胞和其他干细胞的干细胞/祖细胞分化的重要作用。线粒体蛋白合成的抑制导致损伤后脱发。然而，毛囊干细胞（HFSCs）分化过程中线粒体形态和代谢功能的改变以及它们如何影响头发再生尚未得到详细阐述。方法。我们比较了休止期隆起细胞和生长期基质细胞线粒体形态和活性的差异。测定线粒体ROS和超氧化物歧化酶2 （SOD2）的表达水平以评估氧化还原平衡。此外，丙酮酸脱氢酶激酶（PDK）和丙酮酸脱氢酶（PDH）水平在分化过程中表现出能量代谢的变化。为了探讨线粒体代谢对毛发再生的调节作用，我们在拔毛时使用线粒体呼吸抑制剂观察毛发生长情况。结果。在分化过程中，分化细胞的线粒体延长，组织嵴丰富，活性增强。SOD2在分化细胞中氧化还原平衡增强，ROS水平相对稳定。在分化的HFSCs中，PDK升高，而分化的细胞中PDH升高，表明在分化过程中，呼吸从糖酵解转变为氧化磷酸化。毛发拔除时抑制分化毛囊细胞线粒体呼吸抑制毛发再生。结论。HFSCs分化后，线粒体被拉长，嵴更丰富，活性更高，分化细胞的有氧呼吸被激活，能量供应更高。此外，线粒体呼吸功能障碍会延迟受伤后的头发再生。
Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon. Methods. We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking. Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regeneration in vivo. Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair regeneration upon injury.