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SHH INDUCTION OF POST-NATAL HAIR FOLLICLE/HAIR GROWTH

SHH 产后毛囊/毛发生长诱导

基本信息

批准号：
6782738
负责人：
PHILIP L LEOPOLD
金额：
$ 27.29万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2005-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6782738
关键词：
alopecia apoptosis biological signal transduction gene expression gene induction /repression growth /development hair hair follicle hair follicle disorder keratinocyte laboratory mouse

项目摘要

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.

描述：（改编自申请人的摘要）- 本项目的目标建议是更好地了解调节脱发的因素，即与更常见的男性型秃发相关的一个主要社会问题以及更罕见的脱发和化疗。了解脱发并开发新的疗法来预防这种情况，有必要更好地了解毛囊的生物学特性，这是一种独特的主要在产前皮肤中发育和成熟的结构，并在产后皮肤处于上皮和间质复杂的相互作用中。一次发育后，毛囊经历三个阶段的更新周期：（休息）、毛发生长初期（生长）和毛发生长中期（回归）。该提案的重点是音刺猬 (Shh) 信号通路在调节中的作用出生后的毛囊周期。 Shh 函数与一个复杂的途径包括 Ptc（Shh 受体）、Smo（G 蛋白偶联受体）与 Ptc 相互作用），包括 Wnt 类在内的多种信号基因蛋白质和转化生长因子-b 家族。根据已知的在毛囊生长的生长期阶段Shh表达上调，以及初步数据表明，短暂的腺病毒 (Ad) 基因转移载体介导的 Shh 表达诱导毛发生长初期和强健的毛发生长产后皮肤，拟议的研究是基于短暂的假设（不到一周），增强的“Shh”活动起到了生物开关的作用，诱导静息卵泡进入卵泡的毛发生长初期循环，随之而来的毛发生长。建议进行实验来评估两个产后皮肤的假设：（1）Shh 通路的短暂失衡有利于Shh活动诱导毛囊进入生长期随之而来的毛发生长；（2）Shh 诱导毛发生长初期，增强的 Shh 的表达必须在角质形成细胞中，并且对于由此产生的毛囊周期正常，增强的表达必须是暂时的（数天），而不是执着的。