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

Abstract

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.

Probing the Acceptor Active Site Organization of the Human Recombinant β1,4-Galactosyltransferase 7 and Design of Xyloside-based Inhibitors

“…Xyloside analogs have been shown to efficiently induce GAG synthesis bypassing the natural Xyl-substituted core protein of PGs for several decades ( 18 , 19 ). The xyloside-primed GAG chains are usually excreted and show interesting biological functions such as activation of fibroblast growth factor (FGF) signaling ( 20 , 21 ), antithrombotic ( 22 ), tissue regenerating ( 23 ), anti-angiogenic ( 24 ) and anti-proliferative properties ( 25 , 26 ). In addition, several groups have synthesized a series of xyloside analogs as potential inhibitors of GAG synthesis.…”

Effects of C-xylopyranoside derivative on epithelial regeneration in an in vitro 3D oral mucosa model

“…We also showed higher s-GAGs levels in the culture media secreted from XPP-treated cells, basically, in both time-and dosedependent manners, which is consistent with previous studies examining the effect of C-xyloside. 17,19,44) The principal and significant finding of this study is that pharmacologic manipulation during 3DOMM fabrication in the presence of 2 or 10 mM XPP increased the mean and minimal epithelial thickness without disturbing the epithelial structure and differentiation. Of note, when incubated with 2 mM XPP, the epithelial thickness was more consistent as confirmed by its smaller interquartile range, compared with the other groups.…”

“…16) In contrast, this study showed a slight decrease in DS production, which is different from the previous report in which skin keratinocytes were cultured in a monolayer. 44) Thus, OFs, rather than OKs, appear to contribute to the current data using the OKs and OFs co-culture model.…”

Propolis Induces Chondroitin/Dermatan Sulphate and Hyaluronic Acid Accumulation in the Skin of Burned Wound

“…Mentioned functions are connected with GAGs and PGs ability to bind and modulate a vast repertoire of proteins, that is, growth factors, cytokines, morphogens, and enzymes [27]. The most common skin GAG is DS [28] being simultaneously the major glycan in wound fluid [29]. During wound healing DS activates endothelial leukocyte adhesion by stimulation of ICAM-1 [30] or promotion fibroblast growth factor-2, which is also involved in the interaction with hepatocyte growth factor/scatter factor [31], heparin cofactor II, platelet factor 4, fibronectin, and protein C inhibitor [32].…”