Abstract：
Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9-12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis.
摘要：
头发是具有独特多维值的生物丝。在人类中,除了生理影响，脱发和头发相关疾病会影响特征，情感,和社会行为。尽管取得了重大进展，迫切需要探索疗效更高的替代疗法，副作用少，成本低，促进头发生长，治疗头发缺乏。糖皮质激素诱导的亮氨酸拉链(GILZ)是糖皮质激素快速诱导的蛋白质。我们小组和其他许多人的研究表明，GILZ的合成形式，TAT-GILZ,转录反式激活因子和GILZ的融合肽，可以作为炎症反应的有效调节剂，重建和维持体内平衡。在这项研究中,我们调查TAT-GILZ是否可以促进和促进头发生长。对于我们的临床前模型，我们使用了9-12周龄男性BALB/c和裸体(无胸腺，nu/J)小鼠。我们将TAT-GILZ和/或TAT(媒介物)皮内应用于脱毛/无毛小鼠。直接观察,组织学检查,和免疫荧光成像用于评估效果并比较不同的治疗方法。此外,我们测试了两种目前治疗脱发/生长的方法，非那雄胺和米诺地尔,以比较的方式对TAT-GILZ进行最佳评估。我们的结果显示,第一次,合成的TAT-GILZ肽加速了BALB/c脱毛背侧皮肤上的毛发生长，并在无胸腺小鼠的皮肤上诱导了毛发生长。此外,TAT-GILZ能够通过增加包括较高调节性T细胞和糖皮质激素受体在内的抗炎信号来增强毛囊干细胞并重新建立体内平衡。总之,我们的新发现提示,TAT-GILZ合成肽可通过增加毛囊干细胞和重建体内平衡来促进毛发生长.
