Allen Mary, Grachtchouk Marina, Sheng Hong, Grachtchouk Vladimir, Wang Anna, Wei Lebing, Liu Jianhong, Ramirez Angel, Metzger Daniel, Chambon Pierre, Jorcano Jose, Dlugosz Andrzej A
Department of Dermatology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109-0932, USA.
Am J Pathol. 2003 Dec;163(6):2173-8. doi: 10.1016/S0002-9440(10)63574-2.
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 gland 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 functional, secreting their contents directly onto the skin's surface 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.
皮肤中的上皮祖细胞可分化为多个谱系，包括毛囊、相关的皮脂腺以及覆盖其上的表皮；然而，调节皮脂腺发育的信号目前仍知之甚少。我们利用旨在体内阻断或刺激皮肤角质形成细胞中刺猬信号通路的转基因，来测试刺猬信号通路在皮脂腺发育中的潜在作用。抑制刺猬信号通路可选择性地抑制皮脂腺发育，而激活刺猬信号通路则导致皮脂腺的大小和数量显著增加。值得注意的是，异位的刺猬信号还能在通常没有毛囊及相关结构的足垫表皮区域触发皮脂腺的形成。这些异位皮脂腺表达了皮脂腺分化的分子标志物，并且具有功能，它们将其内容物直接分泌到皮肤表面，而不是分泌到毛囊管中。因此，刺猬信号通路在皮脂腺细胞命运决定中起着关键作用，并且是治疗与皮脂腺功能异常相关的皮肤疾病（如痤疮）的潜在靶点。
