Department of Molecular Cell and Developmental Biology, UCLA, Los Angeles, CA, USA.
Pelage Pharmaceuticals, Inc., Los Angeles, CA, USA.
Exp Dermatol. 2021 Apr;30(4):448-456. doi: 10.1111/exd.14307. Epub 2021 Mar 19.
Hair follicle stem cells (HFSCs) are known to be responsible for the initiation of a new hair cycle, but typically remain quiescent for very long periods. In alopecia, or hair loss disorders, follicles can be refractory to activation for years or even permanently. Alopecia can be triggered by autoimmunity, age, chemotherapeutic treatment, stress, disrupted circadian rhythm or other environmental insults. We previously showed that hair follicle stem cells and the hair cycle can be manipulated by regulation of pyruvate entry into mitochondria for subsequent oxidation to fuel the TCA cycle in normal adult mice with typical hair cycling. Here, we present new data from our efforts to develop murine models of alopecia based on environmental triggers that have been shown to do the same in human skin. We found that inhibition of pyruvate transport into mitochondria can accelerate the hair cycle even during refractory hair cycling due to age, repeated chemotherapeutic treatment and stress. Hair cycle acceleration in these alopecia models led to the formation of histologically normal hair follicles within 30-40 days of treatment without any overt signs of toxicity or deleterious effects. Therefore, we propose inhibition of pyruvate entry into mitochondria as a versatile treatment strategy for alopecia in humans.
毛囊干细胞（HFSCs）被认为是启动新的毛发周期的原因，但通常会在很长一段时间内保持静止。在脱发症或毛发缺失症中，毛囊可能会数年甚至永久性地对激活产生抗性。脱发症可能由自身免疫、年龄、化疗治疗、压力、昼夜节律紊乱或其他环境损伤引发。我们之前曾表明，在具有典型毛发周期的正常成年小鼠中，通过调节丙酮酸进入线粒体的过程进行后续氧化以为 TCA 循环供能，可以操纵毛囊干细胞和毛发周期。在这里，我们展示了我们基于已在人类皮肤中显示出相同作用的环境触发因素开发脱发症小鼠模型的新数据。我们发现，抑制丙酮酸向线粒体的转运可以加速毛发周期，即使在由于年龄、反复化疗治疗和压力导致的毛发周期抗性期间也是如此。在这些脱发症模型中，毛发周期的加速导致在 30-40 天的治疗后形成组织学上正常的毛囊，而没有任何明显的毒性或有害影响的迹象。因此，我们提出抑制丙酮酸进入线粒体作为人类脱发症的一种通用治疗策略。
