Exp Dermatol. 2011 Sep;20(9):773-5. doi: 10.1111/j.1600-0625.2011.01319.x. Epub 2011 Jun 24.
Because current skin whitening agents often have insufficient efficacy and side effects, we aim to develop effective and safe therapeutics using RNA interference (RNAi). We established a pigmented human-reconstructed skin model as a first step in the development of novel siRNA-based depigmenting agents. Histological characterization revealed that our model had a similar morphology as normal human skin, expressed keratinocyte differentiation as well as basement membrane markers, and showed a high degree of pigmentation. The utility of the model to study RNAi-induced depigmentation was validated by incorporation of melanocytes transfected with siRNA against tyrosinase, a key enzyme in skin pigmentation. This resulted in a strong reduction in pigmentation and inhibition of melanin transfer proving that siRNA-mediated gene silencing in melanocytes worked successfully in our model. Therefore, this self-made 3D skin model will be a useful and easy tool to validate the whitening potential of candidate genes with a presumed function in melanin synthesis or transfer.
由于目前的皮肤美白剂往往疗效不足且存在副作用，我们旨在使用 RNA 干扰 (RNAi) 开发有效且安全的疗法。我们建立了一个色素沉着的人重建皮肤模型，作为开发新型基于 siRNA 的脱色剂的第一步。组织学特征表明，我们的模型具有与正常人类皮肤相似的形态，表达角蛋白细胞分化以及基底膜标志物，并表现出高度的色素沉着。通过将转染了针对酪氨酸酶的 siRNA 的黑素细胞掺入模型中，验证了该模型在研究 RNAi 诱导的脱色中的用途，酪氨酸酶是皮肤色素沉着的关键酶。这导致色素沉着明显减少，黑色素转移受到抑制，证明 siRNA 介导的黑素细胞中基因沉默在我们的模型中成功进行。因此，这种自制的 3D 皮肤模型将是一种有用且易于使用的工具，可用于验证假定在黑色素合成或转移中具有功能的候选基因的美白潜力。
