Bernerd Françoise
L'Oréal Recherche, Centre C. Zviak, 90, rue du général Roguet, 92583 Clichy, France.
J Soc Biol. 2005;199(4):313-20. doi: 10.1051/jbio:2005032.
The protective role of the skin is provided by the two major compartments of the skin, dermis and epidermis. Both are affected in the long term by consequences of sun exposure such as skin photoaging and cancer development. Characterization of UV-induced skin response at cellular and molecular levels is needed for prevention or correction of these long term effects. The human skin reconstructed in vitro, comprising both a living dermal equivalent and a fully differentiated epidermis represents a predictive tool to characterize wavelength and cell type specific biological damage together with tissular distribution. While UVB directly affects epidermis, inducing DNA lesions and apoptotic sunburn keratinocytes, UVA radiation can directly target the dermal compartment through ROS generation, dermal fibroblasts alterations and extracellular matrix (ECM) modifications. Interactions between the two compartments have also been found, especially for MMP1 induction. In the normal population, photodamage can be repaired through specialized systems. Using skin cells from Xeroderma pigmentosum (XP, a photosensitive and cancer-prone disease), a DNA-repair deficient skin has been developed in vitro. Specific features due to intrinsic XP cell phenotype have been discovered, some of them being indicative of early steps of neoplasia and suggesting a particular role for stroma-epithelium interactions. Finally, human reconstructed skin can be used for approaches designed to regenerate photodamaged skin. The dermal-epidermal junction (DEJ), which is crucial for skin cohesion, is drastically altered in photo-aged skin. The three-dimensional skin model allowed to visualize the improving effects of vitamin C on the DEJ. Modified skin models, lacking one cell type, allowed us to determine the cellular origin of the different markers, their spatial localization, and the respective roles and interactions of keratinocytes and fibroblasts during DEJ formation. All together these studies give a global and tissular view concerning the effects of UV light on skin cells and emphazise the interest of such models for general aspects of cellular biology. By allowing the control of cells used to reconstruct the model and their origin, these studies make it possible to assess the respective role of the two major cellular actors of the skin as well as their interactions. Ongoing research about incorporating other cell types may certainly give rise to even more relevant models.
皮肤的保护作用由皮肤的两个主要部分——真皮和表皮提供。长期来看，二者都会受到阳光照射后果的影响，如皮肤光老化和癌症发展。为预防或纠正这些长期影响，需要在细胞和分子水平上对紫外线诱导的皮肤反应进行表征。体外重建的人体皮肤，包括有活力的真皮替代物和完全分化的表皮，是一种预测工具，可用于表征波长和细胞类型特异性生物损伤以及组织分布。虽然紫外线B直接影响表皮，诱导DNA损伤和凋亡性晒伤角质形成细胞，但紫外线A辐射可通过产生活性氧、改变真皮成纤维细胞和修饰细胞外基质（ECM）直接作用于真皮部分。还发现了两个部分之间的相互作用，尤其是基质金属蛋白酶1的诱导。在正常人群中，光损伤可通过专门的系统修复。利用着色性干皮病（XP，一种光敏且易患癌症的疾病）患者的皮肤细胞，在体外构建了一种DNA修复缺陷型皮肤。已发现了由于内在的XP细胞表型导致的特定特征，其中一些表明了肿瘤形成的早期步骤，并暗示了基质-上皮相互作用的特殊作用。最后，人体重建皮肤可用于旨在再生光损伤皮肤的方法。真皮-表皮连接（DEJ）对皮肤的黏附至关重要，在光老化皮肤中会发生剧烈改变。三维皮肤模型能够观察到维生素C对DEJ的改善作用。缺乏一种细胞类型的改良皮肤模型使我们能够确定不同标志物的细胞来源、它们的空间定位以及角质形成细胞和成纤维细胞在DEJ形成过程中的各自作用和相互作用。所有这些研究提供了关于紫外线对皮肤细胞影响的整体和组织视角，并强调了此类模型在细胞生物学一般方面的意义。通过控制用于重建模型的细胞及其来源，这些研究能够评估皮肤的两个主要细胞成分各自的作用及其相互作用。正在进行的关于纳入其他细胞类型的研究肯定会产生更相关的模型。
