SHH INDUCTION OF POST-NATAL HAIR FOLLICLE/HAIR GROWTH

描述：（改编自申请人的摘要）-本申请的目标 建议是更好地了解调节脱发的因素， 一个主要的社会问题与更常见的男性脱发有关， 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 发展更好地了解生物学的毛囊，一个独特的 主要在产前皮肤中发育和成熟的结构， 出生后的皮肤上皮和间充质的复杂相互作用。一旦 当卵泡发育成熟时，卵泡经历三个阶段的更新周期：休止期 （静止）、生长期（生长）和退化期（退化）。该提案的重点是 Sonic hedgehog（Shh）信号通路在调节 出生后的毛囊周期。Shh函数与一个复合体相关联 包括Ptc（Shh受体）、Smo（G蛋白偶联受体） 与Ptc相互作用），包括Wnt类 蛋白质和转化生长因子-B家族。基于已知的 在卵泡生长的生长期上调Shh表达，和 初步数据表明，瞬时腺病毒（Ad）基因转移 载体介导的Shh表达诱导毛发生长期和健壮的毛发生长， 出生后的皮肤，拟议的研究是基于假设， (less一周以上），增强的Shh活性作为一种生物开关， 诱导静止卵泡进入卵泡生长期 周期，随之而来的头发生长。实验提出评估两个 出生后皮肤的假设：（1）Shh通路的短暂失衡， 有利于Shh活性诱导毛囊进入生长期， （2）对于Shh诱导毛发生长期， Shh的表达必须在角质形成细胞中，并且对于所产生的毛囊， 周期正常，表达增强必须是短暂的（天），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.