SHH INDUCTION OF POST-NATAL HAIR FOLLICLE/HAIR GROWTH

描述：(改编自申请者的摘要)--这一目标 建议更好地了解控制脱发的因素，这是 与更常见的男性型秃顶相关的主要社会问题是 以及更罕见的脱发和化疗。了解脱发 为了开发新的治疗方法来预防这种情况，有必要 更好地了解毛囊的生物学，这是一种独特的 主要在出生前皮肤发育和成熟的结构，并在 出生后皮肤上皮和间充质的复杂相互作用。一次 卵泡发育后，经历了三个阶段的更新周期：端原 (静止期)、生长期(生长)和退化期(回归)。这项提案的重点是 Sonic hedgehog(Shh)信号通路在细胞周期调控中的作用 出生后的毛囊周期。Shh函数与一个复合体关联 包括PTC(Shh受体)、Smo(一种G蛋白偶联受体)的途径 它与PTC)、包括Wnt类在内的各种信号基因相互作用 蛋白质和转化生长因子-b家族。基于已知的 Shh在卵泡生长生长期的表达上调，以及 初步数据表明，瞬时腺病毒(Ad)基因转移 载体介导Shh基因的表达诱导小鼠毛发生长旺盛 出生后皮肤，拟议的研究是基于这样一个假设，即 (不到一周)，增强的Shh活性起到生物开关的作用， 诱导静息卵泡进入卵泡生长期 周期，随之而来的是头发的生长。建议进行实验以评估两个 出生后皮肤假说：(1)Shh通路一过性失衡 促性腺激素活性促进毛囊进入生长期 随之而来的毛发生长；以及(2)Shh诱导生长期，增强 Shh必须在角质形成细胞中表达，并且对于由此产生的卵泡 周期正常，增强的表达必须是瞬时的(天数)，而不是 坚持不懈。

DESCRIPTION: (Adapted from the applicant's abstract) - The goal of this proposal is to understand better the factors that regulate hair loss, which is a major social concern associated with more common male-pattern baldness as well as more rare forms of alopecia and chemotherapy. To understand hair loss and to develop new therapies to prevent this condition, it is necessary to develop better understanding of the biology of the hair follicle, a unique structure that develops and matures mainly in prenatal skin, and cycles in the post-natal skin in a complex interaction of epithelium and mesenchyme. Once developed, the follicles undergo a cycle of renewal in three phases: telogen (resting), anagen (growth), and catagen (regression). This proposal focuses on the role of the Sonic hedgehog (Shh) signaling pathway on modulation of the hair-follicle cycle after birth. Shh function is associated with a complex pathway that includes Ptc (the Shh receptor), Smo (a G-protein coupled receptor that interacts with Ptc), a variety of signaling genes that include Wnt class proteins, and transforming growth factor-b family. Based on the known upregulation of Shh expression in the anagen phase of follicle growth, and preliminary data demonstrating that transient, adenovirus (Ad) gene transfer vector-mediated Shh expression induces anagen and robust hair growth in postnatal skin, the proposed studies are based on the hypothesis that transient (less than a week), enhanced Shh activity functions as a biologic switch that induces resting follicles to enter the anagen growth phase of the follicle cycle, with consequent hair growth. Experiments are proposed to evaluate two hypotheses in postnatal skin: (1) Transient imbalance of the Shh pathway in favor of Shh activity induces hair follicles to enter the anagen phase with consequent hair growth; and (2) for Shh to induce anagen, the enhanced expression of Shh must be in keratinocytes, and for the resulting follicle cycle to be normal, the enhanced expression must be transient (days), not persistent.