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Antibes, France

Serre C.,Global Skin Research Center | Lebleu A.,Global Skin Research Center | Bergeron L.,Global Skin Research Center | Plantivaux A.,Global Skin Research Center | And 3 more authors.
International Journal of Cosmetic Science

Synopsis The stem cell factor (SCF) and its protein-tyrosine kinase receptor KIT are together implicated in the regulation of diverse biological processes and particularly in melanogenesis. Indeed, this signalling pathway controls melanoblast migration from the neural crest during embryogenesis and allows the communication between keratinocytes and melanocytes in the adult. In melanocytes, the binding of SCF to its transmembrane receptor leads to the activation of signalling pathways implicating protein kinases which finally control the expression of pigmentation-related genes. We have developed a biological compound called IV09.007, which we previously described as a modulator of the SCF/KIT signalling pathway with a pro-pigmenting effect. In the present work, we have studied the expression and localization of both SCF and KIT mRNAs and proteins in the skin or skin-derived cell lines. Then, we explored with a microarray approach the ability of IV09.007 to modulate the expression of genes in human keratinocytes and melanocytes in culture. Thereby, we observed the regulation of genes implicated in DNA repair, mainly related to base/nucleotides excision pathways. A modulated transcriptional response was also observed for some genes implicated in the response against oxidative stress, in apoptosis inhibition and in lowering inflammatory immune response. These microarray results predicted a conferred protective effect of IV09.007 and we verified this hypothesis by performing comet assays on UVB-irradiated keratinocytes or melanocytes, to demonstrate the efficacy of IV09.007 on preventing DNA damage. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source

Imbert I.,Global Skin Research Center | Botto J.-M.,Global Skin Research Center | Farra C.D.,ASI R and D | Domloge N.,Global Skin Research Center
Journal of Cosmetic Dermatology

Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments. © 2012 Wiley Periodicals, Inc. Source

McMullen R.L.,International Specialty Products | Bauza E.,Global Skin Research Center | Gondran C.,Global Skin Research Center | Oberto G.,Global Skin Research Center | And 3 more authors.
International Journal of Cosmetic Science

Synopsis Image processing steps and analysis techniques were developed for the quantification of photomicrographs obtained from light and fluorescence microscopy. The substrates examined were either skin cell cultures, such as normal human keratinocytes (NHK) or fibroblasts, or ex vivo skin sections. Examples of the analyses are provided for the comparison of skincare active ingredient treated samples vs. placebo to demonstrate the utility of the methods to quantify and provide numerical data for a procedure that is typically qualitative in nature and based on observations by a histologist. Quantifiable experiments that are discussed include: Fontana Masson staining for melanin expression; Nile red staining to detect cellular lipid droplets; nuclei staining with diamidino-phenylindole (DAPI); and immunofluorescent staining of protein expression with a primary antibody directed against the protein (antigen) and a secondary antibody tagged with a fluorescent dye (Alexa Fluor 488) against the primary antibody. © 2010 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source

Garcia N.,Global Skin Research Center | Gondran C.,Global Skin Research Center | Menon G.,Global Skin Research Center | Mur L.,Corporate Research Center | And 4 more authors.
International Journal of Cosmetic Science

Synopsis One of the main functions of the skin is to protect the organism against environmental threats, such as thermal stress. Aquaporin-3 (AQP3) facilitates water and glycerol transport across cell membranes and therefore regulates osmotic balance in different situations of stress. This mechanism seems to be particularly important for the resistance of different organisms to cold stress. Consequently, we were interested in investigating the effect of cold and osmotic stress on AQP3 expression in normal human keratinocytes. We developed a new active ingredient to stimulate aquaporins in skin and demonstrated the partial restoration of AQP3 expression in keratinocytes transfected with AQP3 siRNA. Moreover, we examined the effect of cold stress on cell morphology and the impact of a pre-treatment with the active ingredient. Our results indicated that induction of AQP3 helped maintain a correct organization of the actin cytoskeleton, preserving cell morphology and preventing cells from rounding. Immunofluorescent staining revealed cytoplasmic localization of AQP3 and its translocation to the cell membrane following osmotic stress. Histological ex vivo studies of skin under different conditions, such as cold environment and tape-stripping, indicated that increase in AQP3 expression appears to be involved in skin protection and showed that the pattern of AQP3 expression was more enhanced in the active ingredient-treated samples. In vivo confocal microscopy by Vivascope showed a generally healthier appearance of the skin in the treated areas. These results attest to the potential value of the active ingredient in optimizing environmental stress resistance and protecting the skin from stratum corneum damage. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie. Source

Bergeron L.,Global Skin Research Center | Gondran C.,Global Skin Research Center | Oberto G.,Global Skin Research Center | Garcia N.,Global Skin Research Center | And 4 more authors.
Journal of Cosmetic Dermatology

Caspase-14, a cysteine endoproteinase belonging to the conserved family of aspartate-specific proteinases, was shown to play an important role in the terminal differentiation of keratinocytes and barrier function of the skin. In the present study, we developed a biofunctional compound that we described as a modulator of caspase-14 expression. Using normal human keratinocytes (NHK) in culture and human skin biopsies, this compound was shown to increase caspase-14 expression and partially reverse the effect of caspase-14-specific siRNA on NHK. Moreover, the increase in filaggrin expression visualized on skin biopsies and the recovery of the barrier structure after tape-stripping indicated that this compound could exhibit a beneficial effect on the skin barrier function. Considering the possible link between caspase-14 and the barrier function, a UVB irradiation on NHK and skin biopsies previously treated with the caspase-14 inducer, was performed. Results indicated that pretreated skin biopsies exhibited less signs of UV damage such as active caspase-3 and cyclobutane pyrimidine dimers (CPDs). Likewise, pretreated NHK were protected from UV-induced genomic DNA damage, as revealed by the Comet Assay. Finally, a clinical test showed a reduction of transepidermal water loss (TEWL) on the treated skin compared with placebo, under UV stress condition, confirming a protecting effect. Taken together, these results strongly suggest that, by increasing caspase-14 expression, the biofunctional compound could exhibit a protective effect on the skin barrier function, especially in case of barrier damage and UV irradiation. © 2012 Wiley Periodicals, Inc. Source

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