Division of Dermatology, University of California, San Diego and Veterans Affairs San Diego Health Care System, San Diego, California, United States of America.
PLoS One. 2011;6(10):e25480. doi: 10.1371/journal.pone.0025480. Epub 2011 Oct 5.
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.
由于 C-木糖苷已被认为是糖胺聚糖 (GAG) 合成的启动子,而硫酸皮肤素 (DS) 等 GAG 是成纤维细胞生长因子 (FGF)-10 作用的有效增强剂,我们研究了 C-木糖苷衍生物(C-β-D-木糖苷-2-羟丙烷,C-木糖苷)是否可以促进培养的正常人角质形成细胞产生 DS,这种情况是如何发生的,以及 C-木糖苷是否也可以刺激 FGF 依赖性细胞迁移和增殖。C-木糖苷处理的角质形成细胞大大增加了总硫酸化 GAG 的分泌。诱导的 GAG 主要是软骨素硫酸盐/硫酸皮肤素 (CS/DS),其中主要分泌的 GAG 是 DS。缺乏木糖基转移酶酶活性的细胞表明,C-木糖苷能够刺激 GAG 合成,而无需添加核心蛋白。与观察到的 DS 增加一致,用 C-木糖苷处理的角质形成细胞显示出对 FGF-10 的迁移增强反应,并分泌到其培养基中的 GAG 促进 FGF-10 依赖性细胞增殖。这些结果表明,C-木糖苷可能通过作为 DS 合成的启动子来增强上皮修复。