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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Indian hedgehog and β-catenin signaling: Role in the sebaceous lineage of normal and neoplastic mammalian epidermis
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Indian hedgehog and β-catenin signaling: Role in the sebaceous lineage of normal and neoplastic mammalian epidermis

机译：印度刺猬和β-catenin信号：在正常和赘生性哺乳动物表皮皮脂谱系中的作用

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摘要

In mammalian epidermis, the level of β-catenin signaling regulates lineage selection by stem cell progeny. High levels of β-catenin stimulate formation of hair follicles, whereas low levels favor differentiation into interfollicular epidermis and sebocytes. In transgenic mouse epidermis, overexpression of β-catenin leads to formation of hair follicle tumors, whereas overexpression of N-terminally truncated Lef1, which blocks β-catenin signaling, results in spontaneous sebaceous tumors. Accompanying overexpression of β-catenin is up-regulation of Sonic hedgehog (SHH) and its receptor. Patched (PTCH/Ptch). In ΔNLef1 tumors Ptch mRNA is up-regulated in the absence of SHH. We now show that PTCH is up-regulated in both human and mouse sebaceous tumors and is accompanied by overexpression of Indian hedgehog (IHH). In normal sebaceous glands IHH is expressed in differentiated sebocytes and the transcription factor GLI1 is activated in sebocyte progenitors, suggesting a paracrine signaling mechanism. PTCH1 and IHH are up-regulated during human sebocyte differentiation in vitro and inhibition of hedgehog signaling inhibits growth and stimulates differentiation. Overexpression of ΔNLef1 up-regulates IHH and stimulates proliferation of undifferentiated sebocytes. We present a model of the interactions between β-catenin and hedgehog signaling in the epidermis in which SHH promotes proliferation of progenitors of the hair lineages whereas IHH stimulates proliferation of sebocyte precursors.
机译：在哺乳动物表皮中，β-catenin信号传导的水平通过干细胞后代调节谱系选择。高水平的β-连环蛋白可刺激毛囊的形成，而低水平的β-catenin则可促进分化为小泡间表皮和皮脂细胞。在转基因小鼠表皮中，β-catenin的过表达导致毛囊肿瘤的形成，而N末端截短的Lef1的过表达会阻断β-catenin的信号传导，导致自发性皮脂瘤。 β-catenin的过度表达伴随着声波刺猬（SHH）及其受体的上调。已修补（PTCH / Ptch）。在不存在SHH的情况下，在ΔNLef1肿瘤中Ptch mRNA上调。我们现在显示，PTCH在人类和小鼠皮脂瘤中均上调，并伴有印度刺猬（IHH）的过度表达。在正常的皮脂腺中，IHH在分化的皮脂细胞中表达，转录因子GLI1在皮脂细胞祖细胞中被激活，提示旁分泌信号传导机制。在体外人皮细胞分化过程中，PTCH1和IHH上调，抑制刺猬信号可抑制生长并刺激分化。 ΔNLef1的过表达上调IHH并刺激未分化皮脂细胞的增殖。我们提出了一种表皮中β-catenin和hedgehog信号之间相互作用的模型，其中SHH促进毛发祖细胞的增殖，而IHH刺激皮脂细胞前体的增殖。

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