[Human skin reconstructed in vitro as a model to study the keratinocyte, the fibroblast and their interactions: photodamage and repair processes].
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.
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Françoise
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D001205:Ascorbic Acid / Q000494:pharmacology; D002450:Cell Communication; D002454:Cell Differentiation; D004249:DNA Damage; D004260:DNA Repair; D020405:Dermis / Q000166:cytology / Q000528:radiation effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000528:radiation effects; D018384:Oxidative Stress; D010787:Photosensitivity Disorders / Q000473:pathology; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species; D012867:Skin / Q000166:cytology* / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects / Q000473:pathology; D017154:Stromal Cells / Q000166:cytology; D023822:Tissue Engineering; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000473:pathology
D016326:Extracellular Matrix Proteins; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid