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-ß-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.

Biological evaluation of a new C-xylopyranoside derivative (C-Xyloside) and its role in glycosaminoglycan biosynthesis.

The mechanical properties of skin are determined primarily by the extracellular matrix of the dermis. These mechanical and biological properties change significantly as a function of age. Key components of the extracellular matrix are proteoglycans, which are molecules composed of a core protein and covalently attached glycosaminoglycans. Proteoglycans and their constituent glycosaminoglycans are involved in many biological processes which are important for dermal function, such as proper formation of the collagen network. A recently developed compound, C-xylopyranoside derivative (C-Xyloside), was designed to mimic ß-xylosides, which are known initiators of glycosaminoglycan biosynthesis. C-Xyloside was found, by several criteria, to act like ß-xylosides, such as in the eliciting of an increase in glycosaminoglycan synthesis by human dermal fibroblasts in culture. This increase may lead to the preservation of matrix integrity and thereby contribute to the firmness of skin. Thus, C-Xyloside may be useful in improving the quality of skin.

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.

A new C-xylopyranoside derivative induces skin expression of glycosaminoglycans and heparan sulphate proteoglycans.

Severe structural changes, including deterioration of the mechanical properties of the dermis, occur during skin aging. It is well known that the degradation of the extracellular matrix contributes to the physical changes in aged skin. Whereas many studies have been devoted to age-related alterations of collagen fibrils, far less attention has been paid to another major family of extracellular matrix components, the glycosaminoglycans (GAGs) and proteoglycans (PGs). Heparan sulphate-proteoglycans, (HS-PGs), a subclass of the PG family that decreases during aging, regulate proliferation and proteolysis as well as matrix adhesion and assembly, and thus, may have important functions in skin. These PGs may represent important targets for dermo-cosmetology in fighting skin aging. The purpose of this study was to demonstrate the potential of a new C-xylopyranoside derivative (C-beta-D-xylopyranoside-2-hydroxy-propane simplified as C-Xyloside) to improve HS-PGs expression in human skin. In an organotypical model of corticosteroid atrophic human skin, characterized by a decrease of PGs expression, treatment with C-Xyloside improved expression of HS-PGs.