Department of Dermatology, Clinic of the Goethe University, Frankfurt am Main, Germany.
Br J Dermatol. 2013 Jul;169(1):156-9. doi: 10.1111/bjd.12271.
Mammalian target of rapamycin (mTOR) signalling integrates signals leading to cellular growth, proliferation and differentiation. Disturbance of this tightly regulated interplay leads to malignancies, as reflected by altered mTOR signalling in epidermal tumours. As psoriatic keratinocytes also show features of perturbed cell growth and differentiation, the question arises as to whether mTOR signalling also plays a role in the pathogenesis of psoriasis.
To investigate the activation status of mTOR signalling components in psoriasis.
Biopsies from lesional and nonlesional skin of patients with psoriasis (n = 10), as well as samples from healthy donors (n = 3), were analysed by immunohistochemistry and Western blot, utilizing antibodies detecting phosphorylated mTOR, phospho-S6 kinase and phospho-S6 ribosomal protein.
We found mTOR and its downstream signalling molecule, the ribosomal protein S6, to be activated in lesional psoriatic skin. While mTOR is activated throughout the whole epidermis, with particularly strong activation in the basal layer, S6 is active in suprabasal layers of differentiating keratinocytes.
Altogether these results suggest a role for mTOR signalling in the epidermal changes leading to the psoriatic phenotype. mTOR inhibition might be a mode of action to explore in developing innovative antipsoriatic drugs.
哺乳动物雷帕霉素靶蛋白（mTOR）信号通路整合了导致细胞生长、增殖和分化的信号。这种紧密调节的相互作用的紊乱会导致恶性肿瘤，如表皮肿瘤中 mTOR 信号的改变所反映的那样。由于银屑病角质形成细胞也表现出细胞生长和分化紊乱的特征，因此 mTOR 信号通路是否也在银屑病的发病机制中发挥作用的问题就出现了。
研究 mTOR 信号通路在银屑病中的激活状态。
通过免疫组织化学和 Western blot 分析来自银屑病患者（n=10）皮损和非皮损皮肤以及健康供体（n=3）的样本，利用检测磷酸化 mTOR、磷酸化 S6 激酶和磷酸化 S6 核糖体蛋白的抗体。
我们发现 mTOR 及其下游信号分子核糖体蛋白 S6 在皮损性银屑病皮肤中被激活。虽然 mTOR 在整个表皮中被激活，特别是在基底层有强烈的激活，但 S6 在分化角质形成细胞的上层中活跃。
总之，这些结果表明 mTOR 信号通路在导致银屑病表型的表皮变化中起作用。mTOR 抑制可能是开发创新型抗银屑病药物的一种作用模式。
