Hedgehog signaling regulates sebaceous gland development
Hedgehog signaling regulates sebaceous gland development
复制标题
DOI：
10.1016/s0002-9440(10)63574-2
复制
发表时间：
2003-12-01
影响因子：
6
通讯作者：
Dlugosz, AA
中科院分区：
文献类型：
--
作者：
Allen, M;Grachtchouk, M;Dlugosz, AA
皮肤中的上皮祖细胞产生多种谱系，包括毛囊、相关的皮脂腺和上覆的表皮；然而，人们对调节皮脂细胞发育的信号知之甚少。我们使用旨在阻断或刺激体内皮肤角质形成细胞中 Hedgehog 信号传导的转基因，测试了 Hedgehog 通路在皮脂发育中的潜在参与。抑制 Hedgehog 通路可以选择性地抑制皮脂细胞的发育，而 Hedgehog 通路的激活则导致皮脂腺的大小和数量显着增加。值得注意的是，异位刺猬信号还触发了足垫表皮皮脂腺的形成，该区域通常没有毛囊和相关结构。这些异位皮脂腺表达皮脂细胞分化的分子标记，并且具有功能，将其内容物直接分泌到皮肤表面而不是进入毛道。因此，Hedgehog 通路在皮脂腺细胞命运决定中发挥着关键作用，并且是治疗与皮脂腺功能异常相关的皮肤疾病（例如痤疮）的潜在靶标。
Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were function, secreting their contents directly onto the skin's surf ace instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.