Nathalie Pineau

Improvement of the dermal epidermal junction in human reconstructed skin by a new c-xylopyranoside derivative

Skin aging entails drastic changes in the extracellular dermal matrix (ECM) and dermal-epidermal junction (DEJ). These biological alterations are reflected in the clinical signs of aged skin. A new C-xylopyranoside derivative, C-beta-D-xylopyranoside-2-hydroxy-propane (C-Xyloside) has been shown to induce neo-synthesis of matrix proteins such as glycosaminoglycans and heparan sulfate proteoglycans. The aim of this study was to assess the effects of C-Xyloside on markers of the dermal epidermal junction. Basement membrane components, collagen IV, collagen VII and laminin 5 as well as sub-epidermal dermal markers, pro-collagen I and fibrillin 1 were analysed using immunohistochemistry in a reconstructed skin model, including a dermal equivalent populated with living fibroblasts. Levels of mRNA of collagen VII alpha1 and collagen IV alpha1 were evaluated in dermal fibroblasts using RT-PCR. The results showed that C-Xyloside significantly induced a higher deposition of basement membrane and DEJ proteins in the reconstructed skin model and increased collagen VII gene expression. These findings indicate that, in addition to stimulating glycosaminoglycan and heparan sulfate proteoglycan expression, C-Xyloside improves the morphogenesis of the whole DEJ, and strongly suggests beneficial effects in aged skin from restoring DEJ integrity.

Exogenous Addition of a C-Xylopyranoside Derivative Stimulates Keratinocyte Dermatan Sulfate Synthesis and Promotes Migration

As C-Xyloside has been suggested to be an initiator of glycosaminoglycan (GAG) synthesis, and GAGs such as Dermatan sulfate (DS) are potent enhancers of fibroblast growth factor (FGF) - 10 action, we investigated if a C-Xylopyranoside derivative, (C-β-D-xylopyranoside-2-hydroxy-propane, C-Xyloside), could promote DS production by cultured normal human keratinocytes, how this occurs and if C-Xyloside could also stimulate FGF-dependent cell migration and proliferation. C-Xyloside-treated keratinocytes greatly increased secretion of total sulfated GAGs. Majority of the induced GAG was chondroitin sulfate/dermatan sulfate (CS/DS) of which the major secreted GAG was DS. Cells lacking xylosyltransferase enzymatic activity demonstrated that C-Xyloside was able to stimulate GAG synthesis without addition to core proteins. Consistent with the observed increase in DS, keratinocytes treated with C-Xyloside showed enhanced migration in response to FGF-10 and secreted into their culture media GAGs that promoted FGF-10-dependent cellular proliferation. These results indicate that C-Xyloside may enhance epithelial repair by serving as an initiator of DS synthesis.