Sato N, Leopold P L, Crystal R G
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
J Natl Cancer Inst. 2001 Dec 19;93(24):1858-64. doi: 10.1093/jnci/93.24.1858.
The Sonic hedgehog (Shh) gene is involved in the initiation of hair growth. We have shown that localized, transient, enhanced expression of the Shh gene in mouse skin mediated by an adenovirus (AdShh) vector accelerates initiation of the anagen (i.e., growth) phase of hair follicle development. Because hair regrowth in chemotherapy-induced alopecia is associated with follicle cell proliferation and active melanogenesis similar to that observed in the anagen phase of normal hair growth, we examined whether AdShh-mediated Shh expression would accelerate hair regrowth in the skin of mice with chemotherapy-induced alopecia.
After establishment of cyclophosphamide-induced alopecia, in either 3- or 7-week-old mice, AdShh or a control vector (AdNull) was delivered to dorsal skin by intradermal injection. Hair regrowth and melanogenesis were assessed by histology and gross morphology. Fisher's exact test was used to compare differences in outcomes between AdShh-treated and control (AdNull-treated or not injected with any vector [naive]) mice. All statistical tests were two-sided.
Northern blot analysis confirmed enhanced Shh expression after AdShh administration in 7-week-old mice. Two weeks after AdShh administration, the injection site (all of five mice) showed large, anagen-phase hair follicles with a normal distribution of melanin. In contrast, both skin treated with AdNull (all of five mice) and skin from naive mice (all of five mice) showed dystrophic hair follicles with irregular distribution of melanin (P<.001 in both comparisons). Gross morphologic observations confirmed that AdShh-treated mice, but not naive mice or AdNull-treated mice, showed skin darkening at the injection site indicative of entry into anagen phase (P<.001 in both comparisons). AdShh treatment of 3-week-old mice with cyclophosphamide-induced alopecia was followed by accelerated hair follicle recovery (19 of 22 mice); such recovery was not observed at this rate in AdNull-treated or naive skin (P<.001 for both comparisons).
Localized, transient, enhanced expression of Shh gene in skin, mediated by an adenovirus vector, might be a future strategy to accelerate hair follicle regrowth after chemotherapy-induced alopecia.
音猬因子（Shh）基因参与毛发生长的起始过程。我们已经表明，由腺病毒（AdShh）载体介导的Shh基因在小鼠皮肤中的局部、短暂、增强表达可加速毛囊发育生长期（即生长阶段）的起始。由于化疗诱导的脱发中的毛发生长与毛囊细胞增殖和活跃的黑素生成有关，这与正常毛发生长的生长期中观察到的情况相似，因此我们研究了AdShh介导的Shh表达是否会加速化疗诱导脱发的小鼠皮肤中的毛发生长。
在3周龄或7周龄小鼠中建立环磷酰胺诱导的脱发后，通过皮内注射将AdShh或对照载体（AdNull）递送至背部皮肤。通过组织学和大体形态学评估毛发生长和黑素生成。使用Fisher精确检验比较AdShh处理组与对照组（AdNull处理组或未注射任何载体的[未处理]小鼠）之间结果的差异。所有统计检验均为双侧检验。
Northern印迹分析证实，在7周龄小鼠中给予AdShh后Shh表达增强。给予AdShh两周后，注射部位（所有五只小鼠）显示出大的生长期毛囊，黑色素分布正常。相比之下，用AdNull处理的皮肤（所有五只小鼠）和未处理小鼠的皮肤（所有五只小鼠）均显示营养不良的毛囊，黑色素分布不规则（两次比较P均<0.001）。大体形态学观察证实，AdShh处理的小鼠而非未处理小鼠或AdNull处理的小鼠在注射部位出现皮肤变黑，表明进入生长期（两次比较P均<0.001）。用AdShh处理3周龄环磷酰胺诱导脱发的小鼠后毛囊恢复加速（22只小鼠中有19只）；在AdNull处理的皮肤或未处理的皮肤中未观察到如此高比例的恢复（两次比较P均<0.001）。
由腺病毒载体介导的Shh基因在皮肤中的局部、短暂、增强表达可能是加速化疗诱导脱发后毛囊再生的未来策略。
