title: Development of a 3D pigmented skin model to evaluate RNAi-induced depigmentation.
abstract: 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.
authors.forename: Mireille
authors.initials: M
authors.lastname: Van Gele
authors.forename: Barbara
authors.initials: B
authors.lastname: Geusens
authors.forename: Reinhart
authors.initials: R
authors.lastname: Speeckaert
authors.forename: Peter
authors.initials: P
authors.lastname: Dynoodt
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanhoecke
authors.forename: Karolien
authors.initials: K
authors.lastname: Van Den Bossche
authors.forename: Jo
authors.initials: J
authors.lastname: Lambert
mesh_terms: D057886:Bleaching Agents; D055785:Gene Knockdown Techniques; D006801:Humans; D021621:Imaging, Three-Dimensional; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012880:Skin Pigmentation / Q000235:genetics* / Q000502:physiology
chemical_list: D057886:Bleaching Agents; D034741:RNA, Small Interfering; D014442:Monophenol Monooxygenase