Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors
Akt activation induces epidermal hyperplasia and proliferation of epidermal progenitors
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DOI：
10.1038/sj.onc.1210274
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发表时间：
2007-07-19
期刊：
影响因子：
8
通讯作者：
Nakano, T.
中科院分区：
文献类型：
--
作者：
Murayama, K.;Kimura, T.;Nakano, T.
各种常见的信号传导途径维持组织干细胞，包括Notch和Wnt/β-连环蛋白信号。磷脂酰肌醇3激酶（PI 3 K）/Akt信号传导调节培养物中几种干细胞的“干性”，特别是在维持胚胎干细胞和神经干细胞以及从原始生殖细胞衍生胚胎生殖细胞中。我们研究了表达Akt-Mer融合蛋白的转基因小鼠表皮细胞中Akt信号传导的作用，该融合蛋白的激酶活性通过4-羟基他莫昔芬（4 OHT）治疗被条件性激活。将4 OHT局部应用于转基因小鼠的成年皮肤诱导静息期毛囊中的新毛发生长。此外，小鼠表现出毛囊间表皮（IFE）和毛囊的增生，这可能分别是由IFE基底层和毛囊外根鞘中的角质形成细胞广泛增殖引起的。在4 OHT处理的转基因小鼠中，祖细胞群体持续增加。我们的研究结果表明，PI 3 K/Akt信号转导诱导表皮增生和表皮祖细胞的增殖。
Various common signaling pathways maintain tissue stem cells, including Notch and Wnt/beta-catenin signals. Phosphoinositide3 kinase (PI3K)/Akt signaling regulates the 'stemness' of several stem cells in culture, specifically in maintaining embryonic stem and neural stem cells, and in deriving embryonic germ cells from primordial germ cells. We examined the effect of Akt signaling in epidermal cells in transgenic mice expressing an Akt-Mer fusion protein whose kinase activity was conditionally activated by treatment with 4-hydroxytamoxifen (4OHT). The topical application of 4OHT to adult skin of the transgenic mice induced new hair growth in resting phase follicles. In addition, the mice showed hyperplasia in interfollicular epidermis (IFE) and hair follicles, which was presumably caused by the extensive proliferation of keratinocytes in basal layer of IFE and outer root sheath of hair follicles, respectively. The progenitor cell population increased consistently in 4OHT-treated transgenic mice. Our results show that PI3K/Akt signaling induces epidermal hyperplasia and proliferation of epidermal progenitors.